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Journal articles on the topic 'Naine T'

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Published: 4 June 2021
Last updated: 1 February 2022

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1

Rodrigues Filho, Vagner A., Júlio C. L. Neves, Sérgio L. R. Donato, and Bruno V. C. Guimarães. "Model for determining nutritional and non-nutritional limitations of Grande Naine banana in the Brazilian semiarid region." Revista Brasileira de Engenharia Agrícola e Ambiental 25, no. 8 (August 2021): 538–46. http://dx.doi.org/10.1590/1807-1929/agriambi.v25n8p538-546.

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ABSTRACT Plant nutrition is essential in attaining higher yields; however, non-nutritional factors play a major role in limiting crop yield. This study aimed to model and determined nutritional and non-nutritional limitations of Grande Naine banana grown in Ceará and Bahia states, Brazil, based on nutritional balance and equilibrium. The data used in this study were collected between 2010 and 2017 from two farms, located in Missão Velha, Ceará (7° 35’ 90” S and 39° 21’ 17” W, and 442 m of altitude), and Ponto Novo, Bahia (10º 51’ 46” S and 40º 08’ 01” W, and 342 m of altitude). Plots with yields greater than the average plus 0.5 standard deviations were defined as high-yielding populations (HYP) and used as a reference population to establish the norms. Plots with yields below this limit, low-yielding populations (LYP), were used for nutritional diagnosis. The database was divided into four. The first and second databases, from the area located in Missão Velha, contained 46 samples from a reference population with a yield greater than 58.84 t ha-1 per year, and 104 samples from an LYP, respectively. The third and four databases, from the area located in Ponto Novo, contained 19 samples from a reference population with a yield greater than 76.12 t ha-1 per year, and 46 samples from an LYP, respectively. Nutritional factors limited Grande Naine banana yield in Ceará and Bahia by 11.17 and 14.79%, while non-nutritional factors limited by 30.11 and 29.41%, respectively. In Grande Naine banana, non-nutritional factors are more yield-limiting than nutritional factors.
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2

Sousa, Valdemício Ferreira de, Marcos Emanuel da Costa Veloso, Lúcio Flavo Lopes Vasconcelos, Valdenir Queiroz Ribeiro, Valdomiro Aurélio Barbosa de Souza, and Boanerges Siqueira d'Albuquerque Junior. "Nitrogênio e potássio via água de irrigação nas características de produção da bananeira 'Grand Naine'." Pesquisa Agropecuária Brasileira 39, no. 9 (September 2004): 865–69. http://dx.doi.org/10.1590/s0100-204x2004000900005.

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O objetivo deste trabalho foi avaliar o efeito do nitrogênio e do potássio, aplicados via água de irrigação por microaspersão, sobre as características de produção da bananeira, cv. Grand Naine. O delineamento utilizado foi o de blocos casualizados, com quatro repetições. Os tratamentos consistiram de 30, 180, 300, 420 e 570 kg ha-1 ano-1 de N e de 55, 330, 550, 770 e 1.045 kg ha-1 ano-1 de K2O, e testemunha, sem adubação, totalizando onze tratamentos, de acordo com o modelo da matriz experimental de Plan Puebla III. Foram avaliadas as características: massa média de fruto, massa média de cacho e produtividade, referentes ao primeiro e segundo ciclos de produção. No primeiro e segundo ciclos, a massa média de fruto, a massa média de cacho e a produtividade foram influenciadas apenas pelas doses de potássio. Os maiores valores de massa média de fruto (253,47 g), massa média de cacho (28 kg) e produtividade (55,42 t ha-1), no primeiro ciclo, foram obtidos com a aplicação de 938,31, 665,38 e 665,27 kg ha-1 de K2O, respectivamente. No segundo ciclo, os maiores valores em relação à massa média de fruto (174, 22 g), massa média de cacho (32,04 kg) e produtividade (60,08 t ha-1) foram alcançados com a aplicação de 725,50, 907,50 e 933,33 kg ha-1 de K2O, respectivamente. Não houve resposta das características avaliadas ao nitrogênio.
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3

Bengaly, Zakaria, Peter-Henning Clausen, Hamidou Boly, Augustin Kanwé, and Gérard Duvallet. "Comparaison de la trypanosomose expérimentale chez certaines races de petits ruminants au Burkina Faso." Revue d’élevage et de médecine vétérinaire des pays tropicaux 46, no. 4 (April 1, 1993): 563–70. http://dx.doi.org/10.19182/remvt.9410.

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Pour comparer leurs degrés respectifs de sensibilité à l'égard de la trypanosomose, 24 moutons et chèvres de race naine Djallonké, et 16 moutons et chèvres Peul du Sahel, ont été inoculés avec des souches de Trypanosoma vivax et de Trypanosoma congolense. Un animal de chaque race a servi de témoin. Une anémie est observée chez tous les animaux inoculés. Pour l'infection à T. vivax, 1 chèvre Djallonké sur 6, 3 chèvres sur 4 et 2 moutons sur 4 de race Peul du Sahel sont morts en 16 semaines d'expérimentation. Une seule mortalité sur 4 est enregistrée dans le lot des moutons Peul du Sahel, pour l'infection à T. congolense. Les chutes de poids et de concentration leucocytaire observées ne diffèrent pas significativement entre Djallonké et Peul du Sahel durant 8 semaines. Cette étude montre une bonne résistance des moutons et chèvres Djallonké à l'infection à T. vivax. Par contre, il n'y a pas de différence significative entre les deux races de moutons et de chèvres infectés à T.congolense.
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4

GOENAGA, R., and H. IRIZARRY. "YIELD OF BANANA GROWN WITH SUPPLEMENTAL DRIP-IRRIGATION ON AN ULTISOL." Experimental Agriculture 34, no. 4 (October 1998): 439–48. http://dx.doi.org/10.1017/s0014479798004062.

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A three-year study was conducted on an Ultisol to determine the water requirement, yield and fruit-quality traits of three ratoon crops (R1, R2, R3) of ‘Grande Naine’ banana (Musa acuminata Colla, AAA group) subjected to four levels of irrigation. The irrigation treatments were based on Class A pan factors ranging from 0.0 (rainfed) to 1.0 in increments of 0.25. When needed, drip irrigation was supplied three times a week on alternate days. Results showed significant (p < 0.01) irrigation treatment and crop effects on bunch weight, yield, bunch mean hand weight, weight and fruit diameter of the third and last hands, and length of fruits of the third hand. Highest marketable yield (47.9 t ha−1) was obtained from the R2 crop with water application according to a pan factor of 1.0. It was concluded that irrigating the crop according to a pan factor of 1.0 was sufficient to justify the investment of a drip-irrigation system for a farm in the mountain region.
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5

Teixeira, Luiz Antonio Junqueira, Bernardo Van Raij, and José Emílio Bettiol Neto. "Estimativa das necessidades nutricionais de bananeiras do subgrupo Cavendish cultivadas no Estado de São Paulo." Revista Brasileira de Fruticultura 30, no. 2 (June 2008): 540–45. http://dx.doi.org/10.1590/s0100-29452008000200047.

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A acumulação na planta e a exportação de nutrientes pela colheita dos cachos são alguns dos fatores que determinam a necessidade de adubação para a cultura da bananeira. Visando a estimar as quantidades de nutrientes acumulados e exportados por bananeiras do subgrupo Cavendish, nas condições de cultivo do Estado de São Paulo, foram considerados 293 registros de um banco de dados contendo teores de N, P, K, Ca, Mg, S, B, Cu, Fe, Mn e Zn em frutos e em engaços e massa dos cachos das cultivares Grande Naine e Nanicão. Esses registros provieram de experimentos de adubação realizados no Planalto Paulista e no Vale do Ribeira, em áreas irrigadas e de sequeiro, durante sete ciclos de cultivo, variando fontes, doses e formas de aplicação de fertilizantes. Para produzir 40 t ha-1, em média, o nutriente exportado pelos cachos em maior quantidade foi o K (182 kg ha-¹ ) seguido pelo N (68 kg ha-¹), Mg (10 kg ha-¹), P (8 kg ha-¹), Ca (6 kg ha-¹), S (3 kg ha-¹), Mn (191 g ha-¹), Fe (147 g ha-¹), B (89 g ha-¹), Zn (68 g ha-¹) e Cu (25 g ha-¹). A recomendação de adubação para bananeira para o Estado de São Paulo, aparentemente, subestima a necessidade de K na implantação da cultura e preconiza doses de N muito superiores à exportação de N pelos cachos. Para P, a recomendação está coerente com as necessidades estimadas para a cultura.
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6

Ko, Dong-Woo, and Jung-Jin Yang. "New Exploration to Identify the Naive T Cell-Specific Gene Using Gene Similarity." Journal of Korean Institute of Information Technology 18, no. 2 (February 28, 2020): 33–43. http://dx.doi.org/10.14801/jkiit.2020.18.2.33.

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7

Pereira, Lair Victor, Sebastião de Oliveira e. Silva, Elio José Alves, and Carlos Ramirez de Rezende e. Silva. "Avaliação de cultivares e hibridos de bananeira em lavras, MG." Ciência e Agrotecnologia 27, no. 1 (February 2003): 17–25. http://dx.doi.org/10.1590/s1413-70542003000100002.

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Avaliaram-se os genótipos de bananeira Nam, Pioneira, Caipira, Prata Anã, Grande Naine, SH36-40, FHIA 18, FHIA 01 e PV 03-44, em condições de sequeiro na região sul de Minas Gerais, com o objetivo de identificar os mais produtivos e com melhor adaptação edafoclimática, em comparação com as cultivares Prata e Prata Anã, tradicionalmente cultivadas nessa região. O ensaio foi conduzido na Fazenda Experimental da EPAMIG, em Lavras, no período de 1997 a 1999. Cada genótipo foi plantado em blocos de 50 plantas, no espaçamento 3,0 x 3,0 m, sendo a parcela útil as 24 plantas centrais e uma por repetição. O híbrido SH36-40 foi superior aos demais em peso médio dos cachos (16,56 kg), frutos (171,00 g), diâmetro (4,21 cm) e comprimento dos frutos (17,64 cm) nos três primeiros ciclos. Isso corresponde a um rendimento de 18,5 t/ha, cerca de duas vezes maior que a produção das cultivares Prata Anã, Pioneira, Nam, Caipira e três vezes maior que a do híbrido PV 03-44. O híbrido SH 36-40 apresentou, ainda, porte médio de 2,75 m, ciclo em torno de 17,5 meses e o menor período da emissão à colheita do cacho, inferior a 4,83 meses para as plantas-mãe, filha e neta. Esse híbrido apresentou também um menor e mais tardio perfilhamento. Os híbridos SH 36-40 e FHIA 01 apresentaram os maiores incrementos nos pesos dos cachos e dos frutos do primeiro para o terceiro ciclo. As cultivares Caipira, Prata Anã, Pioneira e Nam produziram cachos com peso médio inferior a 9,0 kg e o híbrido PV0344, inferior a 6,0 kg. A cv. Caipira foi a mais tardia, com um ciclo em torno de 22 meses e a Prata Anã e Pioneira, as mais precoces, com cerca de 16,6 meses no primeiro ciclo e 15,5 no segundo e terceiro ciclos.
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8

Helft, Julie, Alexandra Jacquet, Nathalie T. Joncker, Isabelle Grandjean, Guillaume Dorothée, Adrien Kissenpfennig, Bernard Malissen, Polly Matzinger, and Olivier Lantz. "Antigen-specific T-T interactions regulate CD4 T-cell expansion." Blood 112, no. 4 (August 15, 2008): 1249–58. http://dx.doi.org/10.1182/blood-2007-09-114389.

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Abstract The regulation of CD4 T-cell numbers during an immune response should take account of the amount of antigen (Ag), the initial frequency of Ag-specific T cells, the mix of naive versus experienced cells, and (ideally) the diversity of the repertoire. Here we describe a novel mechanism of T-cell regulation that potentially deals with all of these parameters. We found that CD4 T cells establish a negative feedback loop by capturing their cognate major histocompatibility class (MHC)/peptide complexes from Ag-presenting cells and presenting them to Ag-experienced CD4 T cells, thereby inhibiting their recruitment into the response while allowing recruitment of naive T cells. The inhibition is Ag specific, begins at day 2 (long before Ag disappearance), and cannot be overcome by providing new Ag-loaded dendritic cells. In this way, CD4 T-cell proliferation is regulated in a functional relationship to the amount of Ag, while allowing naive T cells to generate repertoire variety.
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9

Gerlach, Carmen, Jeroen W. J. van Heijst, Erwin Swart, Daoud Sie, Nicola Armstrong, Ron M. Kerkhoven, Dietmar Zehn, Michael J. Bevan, Koen Schepers, and Ton N. M. Schumacher. "One naive T cell, multiple fates in CD8+ T cell differentiation." Journal of Experimental Medicine 207, no. 6 (May 17, 2010): 1235–46. http://dx.doi.org/10.1084/jem.20091175.

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The mechanism by which the immune system produces effector and memory T cells is largely unclear. To allow a large-scale assessment of the development of single naive T cells into different subsets, we have developed a technology that introduces unique genetic tags (barcodes) into naive T cells. By comparing the barcodes present in antigen-specific effector and memory T cell populations in systemic and local infection models, at different anatomical sites, and for TCR–pMHC interactions of different avidities, we demonstrate that under all conditions tested, individual naive T cells yield both effector and memory CD8+ T cell progeny. This indicates that effector and memory fate decisions are not determined by the nature of the priming antigen-presenting cell or the time of T cell priming. Instead, for both low and high avidity T cells, individual naive T cells have multiple fates and can differentiate into effector and memory T cell subsets.
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10

Klein, Dieter. "HIV latency in naive T cells." Trends in Molecular Medicine 7, no. 7 (July 2001): 285. http://dx.doi.org/10.1016/s1471-4914(01)02071-8.

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11

Lewis, Marie, John F. Tarlton, and Stephen Cose. "Memory versus naive T‐cell migration." Immunology & Cell Biology 86, no. 3 (November 13, 2007): 226–31. http://dx.doi.org/10.1038/sj.icb.7100132.

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12

Swain, Susan L., Michael Croft, Caroline Dubey, Laura Haynes, Paul Rogers, Xiaohong Zhang, and Linda M. Bradley. "From Naive to Memory T Cells." Immunological Reviews 150, no. 1 (April 1996): 143–67. http://dx.doi.org/10.1111/j.1600-065x.1996.tb00700.x.

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13

Papatriantafyllou, Maria. "mTOR lullabies for naive T cells." Nature Reviews Immunology 11, no. 9 (August 5, 2011): 572–73. http://dx.doi.org/10.1038/nri3047.

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14

Sanders, Martin E., Malegapuru W. Makgoba, and Stephen Shaw. "Human naive and memory T cells." Immunology Today 9, no. 7-8 (January 1988): 195–99. http://dx.doi.org/10.1016/0167-5699(88)91212-1.

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15

Kimmig, Sonja, Grzegorz K. Przybylski, Christian A. Schmidt, Katja Laurisch, Beate Möwes, Andreas Radbruch, and Andreas Thiel. "Two Subsets of Naive T Helper Cells with Distinct T Cell Receptor Excision Circle Content in Human Adult Peripheral Blood." Journal of Experimental Medicine 195, no. 6 (March 18, 2002): 789–94. http://dx.doi.org/10.1084/jem.20011756.

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During ageing thymic function declines and is unable to meet the demand for peripheral T helper (Th) cell replenishment. Therefore, population maintenance of naive Th cells must be at least partly peripherally based. Such peripheral postthymic expansion of recent thymic emigrants (RTEs) during ageing consequently should lead to loss or dilution of T cell receptor excision circles (TRECs) from a subset of naive T cells. We have identified two subsets of naive Th cells in human adult peripheral blood characterized by a striking unequal content of TRECs, indicating different peripheral proliferative histories. TRECs are highly enriched in peripheral naive CD45RA+ Th cells coexpressing CD31 compared with peripheral naive CD45RA+ Th cells lacking CD31 expression, in which TRECs can hardly be detected. Furthermore we show that CD31−CD45RA+ Th cells account for increasing percentages of the naive peripheral Th cell pool during ageing but retain phenotypic and functional features of naive Th cells. As CD31 is lost upon T cell receptor (TCR) engagement in vitro, we hypothesize that TCR triggering is a prerequisite for homeostatically driven peripheral postthymic expansion of human naive RTEs. We describe here the identification of peripherally expanded naive Th cells in human adult blood characterized by the loss of CD31 expression and a highly reduced TREC content.
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16

Tough, D. F., and J. Sprent. "Turnover of naive- and memory-phenotype T cells." Journal of Experimental Medicine 179, no. 4 (April 1, 1994): 1127–35. http://dx.doi.org/10.1084/jem.179.4.1127.

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On the basis of their surface markers, T lymphocytes are divided into subsets of "naive" and "memory cells". We have defined the interrelationship and relative life spans of naive and memory T cells by examining the surface markers on murine T cells incorporating bromodeoxyuridine, a DNA precursor, given in the drinking water. Three findings are reported. First, using a new method we show that the release of newly formed naive T cells from the unmanipulated thymus is very low (confirming the findings of others with surgical approaches). Second, in thymectomized mice, T cells with a naive phenotype remain in interphase for prolonged periods; however, some of these cells divide and retain (or regain) their "naive" markers. Third, most T cells with a memory phenotype divide rapidly, but others remain in interphase for many weeks. Collectively, the data indicate that long-lived T cells have multiple phenotypes and contain a mixture of memory cells, naive (virgin) cells, and memory cells masquerading as naive cells.
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17

Fagnoni, Francesco F., Rosanna Vescovini, Giovanni Passeri, Giovanni Bologna, Mario Pedrazzoni, Giampaolo Lavagetto, Amos Casti, Claudio Franceschi, Mario Passeri, and Paolo Sansoni. "Shortage of circulating naive CD8+ T cells provides new insights on immunodeficiency in aging." Blood 95, no. 9 (May 1, 2000): 2860–68. http://dx.doi.org/10.1182/blood.v95.9.2860.009k35_2860_2868.

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Clinical observations indicate that elderly people are prone to severe, often lethal infectious diseases induced by novel pathogens. Since the ability to mount primary immune responses relies on the availability of naive T cells, the circulating naive T-cell reservoir was evaluated throughout the human life span. Naive T cells were identified as CD95− T lymphocytes for their phenotypic and functional features. Indeed, the lack of CD95 marker is sufficient to identify a population of naive T cells, as defined by coincidence with previously characterized CD45RA+ CD62L+ T cells. Naive CD95− T cells, as expected, require a costimulatory signal, such as CD28, to optimally proliferate after anti-CD3 stimulation. Cytofluorimetric analysis of circulating T lymphocytes from 120 healthy subjects ranging in age from 18 to 105 years revealed that naive T cells decreased sharply with age. The younger subjects had a naive T-lymphocyte count of 825 ± 48 cells/μL, and the centenarians had a naive T-lymphocyte count of 177 ± 28 cells/μL. Surprisingly, the naive T-cell count was lower in CD8+than in CD4+ subsets at any age, and the oldest individuals were almost completely depleted of circulating naive CD8+ T cells (13 ± 4 cells/μL). Concomitantly, a progressive expansion of CD28− T cells occurs with age, which can be interpreted as a compensatory mechanism. These data provide new insights into age-related T-cell–mediated immunodeficiency and reveal some analogies of T-cell dynamics between advanced aging and human immunodeficiency virus (HIV) infection. In conclusion, the exhaustion of the naive CD8+ T-cell reservoir, which has never been reported before, suggests that this T-cell pool is a major target of the aging process and may define a parameter possibly related to the life span of humans.
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18

Tanchot, Corinne, Henrique Veiga Fernandes, and Benedita Rocha. "The organization of mature T–cell pools." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 355, no. 1395 (March 29, 2000): 323–28. http://dx.doi.org/10.1098/rstb.2000.0569.

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To deal with exogenous pathogens the peripheral T–cell compartment requires diverse repertoires (as those of naive cells) and efficient responses, the latter dependent on the persistence of memory cells. In the present work we show that (i) naive and memory cells differ in the type of interactions required for survival and division; (ii) they are segregated into independent ecological niches; (iii) that the size of each niche is controlled by independent homeostatic mechanisms; and (iv) that naive T cells do not have intrinsic life spans, surviving in the absence of thymus output but being continuously substituted by thymus export. The independent homeostatic regulation of the naive and memory T–cell pools guarantees the maintenance of versatile and efficient repertoires throughout life as well as the persistence of the naive T–cell pool after the thymus atrophies at puberty.
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19

Akinola, L. A. F., and C. F. Nwanochi. "Evaluation of calcium and vitamin D3 in cassava-based diets on internal and external qualities of chicken eggs." Nigerian Journal of Animal Production 48, no. 2 (March 2, 2021): 90–100. http://dx.doi.org/10.51791/njap.v48i2.2926.

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The aim of this study was to evaluate the effect of calcium and vitamin D3 in cassava-based layers' diet on the external and internal qualities of egg. One hundred and thirty-five, ISA brown layers aged 54 weeks were assigned randomly to 9 treatment (T) combinations with three replicates in a 3×3 factorial arrangement in a completely randomized design. Each replicate had five hens while the diets were: T1 = 3.5% Ca and 1000 IU vitamin D3 , T2 = 3.5% Ca and 2000 IU vitamin D3 , T3 = 3.5% Ca and 3000 IU vitamin D3 , T4 = 4.5% Ca and 1000 IU vitamin D3 , T5 = 4.5% Ca and 2000 IU vitamin D3 , T6 = 4.5% Ca and 3000 IU vitamin D3 , T7 = 5.5% Ca and 1000 IU vitamin D3 , T8 = 5.5% Ca and 2000 IU vitamin D3 , and T9 = 5.5% Ca and 3000 IU vitamin D3 . After 12 weeks, two eggs were collected per replicate to assess the 3 external and internal egg qualities. The increasing levels of calcium and vitamin D3 had no effect on the external and internal qualities of the eggs. From the result, hens that were fed 4.5% and 5.5% Ca recorded highest shell thickness. The interaction of calcium and vitamin D3 affected the shell thickness with hens fed diet T5 (4.5% Ca with 2000 IU) recording the thickest egg shell while T2 (3.5% Ca with 2000 IU) recorded the lowest. It was therefore concluded that 4.5% and 5.5% dietary calcium, 1000 IU and 3000 IU vitamin D3 were best when used individually in the diet for hens while T5 (4.5% calcium with 2000 IU) favoured eggs shell thickness for hens aged 54 -66 weeks. Une augmentation de la production des chevres dans les zones tropicales a conduit à une concurrence continue avec les humains pour la nourriture car la plupart des protéines étant donné les aliments conventionnels (gâteau à l'arachide, gâteau palmiste, soja) entre autres sont de plus en plus rares et coûteux, il est donc nécessaire de trouver du matériel d'alimentation non conventionnel qui peut remplacer considérablement les aliments conventionnels sans conséquences négatives sur l'animal. Ce travail de recherche visait donc les caractéristiques de performance des chèvres naines d'Afrique de l'Ouest (le 'WAD') nourries de grainesde testaà base de cacao (le 'CST') en remplacement du supplément de concentré de gâteau au palmiste à un régime basal d'herbe. Douze chèvres naines d'Afrique de l'Ouest de 15 à 16 mois avec un poids moyen de 16.5 kg ont été utilisées pour l'expérience. Ils ont été attribués au hasard à trois régimes concentrés de telle sorte que 0%, 50%, 100% étaient pour le groupe A, B et C, respectivement du gâteau de palmiste (le 'PKC') ont été remplacés par des testicules de graines de cacao (le 'CST'). Chacun des trois groupes a été élevé sur l'un des suppléments de concentré alimentés à un régime basal de l'herbe (Cynodonnlemfuensis). L'expérience a duré six semaines, au cours de laquelle deux semaines ont été utilisées pour acclimatiser les animaux aux cages. Le résultat de l'expérience a montré une différence significative (P<0.05) dans l'apport alimentaire global moyen, le poids gagné et le ratio de conversion des aliments pour animaux parmi les traitements. Le gain de poids quotidien moyen et le gain de poids global parmi les groupes de traitement étaient significativement différence (P<0.05). Les chèvres nourries de régime B utilisé l'alimentation mieux avec un gain de poids de 2539.96 g suivie par ceux de l'alimentation C avec gain de poids de 1969.94 g. L'inclusion de graines de testa à base de cacao de 50 % à 100 % de remplacement pour le gâteau au palmiste améliore la croissance de la chèvre naine d'Afrique de l'Ouest.
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20

Zhao, Chunfang, and Joanna D. Davies. "A peripheral CD4+ T cell precursor for naive, memory, and regulatory T cells." Journal of Experimental Medicine 207, no. 13 (December 13, 2010): 2883–94. http://dx.doi.org/10.1084/jem.20100598.

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Mechanisms that control the size of the T cell pool, the ratio between naive cells and memory cells, the number and frequency of regulatory T cells, and T cell receptor (TCR) diversity are necessary to maintain immune integrity and avoid disease. We have previously shown that a subset of naive CD4+ T cells, defined by the expression on their surface of a very low density of CD44 (CD44v.low cells), can inhibit wasting and wasting-associated lymphopenia in mice with cancer. In this study, we further investigate the properties of CD44v.low cells and show that they are significantly more efficient than the remaining naive (CD44low or CD44int) and memory CD4+ cell subsets in reconstituting the overall size of the CD4+ T cell pool, creating a T cell pool with a diverse TCR repertoire, generating regulatory T cells that express forkhead box P3 (FoxP3), and promoting homeostatic equilibrium between naive, memory, and Foxp3+ regulatory T cell numbers. T cell population reconstitution by CD44v.low cells is thymus independent. Compared with CD44int cells, a higher percentage of CD44v.low cells express B cell leukemia/lymphoma 2, interleukin-7 receptor, and CD5. The data support a key role for CD4+ CD44v.low cells as peripheral precursors that maintain the integrity of the CD4+ T cell pool.
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21

Mehlhop-Williams, Erin R., and Michael J. Bevan. "Memory CD8+ T cells exhibit increased antigen threshold requirements for recall proliferation." Journal of Experimental Medicine 211, no. 2 (February 3, 2014): 345–56. http://dx.doi.org/10.1084/jem.20131271.

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A hallmark of immunological memory is the ability of previously primed T cells to undergo rapid recall responses upon antigen reencounter. Classic work has suggested that memory T cells proliferate in response to lower doses of antigen than naive T cells and with reduced requirements for co-stimulation. In contrast to this premise, we observed that naive but not memory T cells proliferate in vivo in response to limited antigen presentation. To reconcile these observations, we tested the antigen threshold requirement for cell cycle entry in naive and central memory CD8+ T cells. Although both naive and memory T cells detect low dose antigen, only naive T cells activate cell cycle effectors. Direct comparison of TCR signaling on a single cell basis indicated that central memory T cells do not activate Zap70, induce cMyc expression, or degrade p27 in response to antigen levels that activate these functions in naive T cells. The reduced sensitivity of memory T cells may result from both decreased surface TCR expression and increased expression of protein tyrosine phosphatases as compared with naive T cells. Our data describe a novel aspect of memory T cell antigen threshold sensitivity that may critically regulate recall expansion.
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Geiger, Rebekka, Thomas Duhen, Antonio Lanzavecchia, and Federica Sallusto. "Human naive and memory CD4+ T cell repertoires specific for naturally processed antigens analyzed using libraries of amplified T cells." Journal of Experimental Medicine 206, no. 7 (June 29, 2009): 1525–34. http://dx.doi.org/10.1084/jem.20090504.

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The enormous diversity of the naive T cell repertoire is instrumental in generating an immune response to virtually any foreign antigen that can be processed into peptides that bind to MHC molecules. The low frequency of antigen-specific naive T cells, their high activation threshold, and the constrains of antigen-processing and presentation have hampered analysis of naive repertoires to complex protein antigens. In this study, libraries of polyclonally expanded naive T cells were used to determine frequency and antigen dose–response of human naive CD4+ T cells specific for a variety of antigens and to isolate antigen-specific T cell clones. In the naive repertoire, T cells specific for primary antigens, such as KLH and Bacillus anthracis protective antigen, and for recall antigens, such as tetanus toxoid, cytomegalovirus, and Mycobacterium tuberculosis purified protein derivative, were detected at frequencies ranging from 5 to 170 cells per 106 naive T cells. Antigen concentrations required for half-maximal response (EC50) varied over several orders of magnitude for different naive T cells. In contrast, in the memory repertoire, T cells specific for primary antigens were not detected, whereas T cells specific for recall antigens were detected at high frequencies and displayed EC50 values in the low range of antigen concentrations. The method described may find applications for evaluation of vaccine candidates, for testing antigenicity of therapeutic proteins, drugs, and chemicals, and for generation of antigen-specific T cell clones for adoptive cellular immunotherapy.
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Hang, Junjie, Lixia Wu, and Kequn Xu. "The clinical implication of CD45RA+ naive T cells and CD45RO+ memory T cells in advanced pancreatic cancer: A proxy for tumor biology and outcome prediction." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 196. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.196.

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196 Background: Naive and memory T cells play a pivotal role in solid tumor pathogenesis but their role in pancreatic cancer progression remains elusive. Thus, we aimed to investigate their clinical potential in advanced pancreatic cancer (APC). Methods: Flow cytometry was performed to evaluate the level of peripheral naive and memory T cells from APC patients. Interrelationships between naive, memory T cells and clinicopathological variables were evaluated using pearson’s correlation. The prognostic impact of naive and memory T cells were assessed by Kaplan-Meier analysis and Cox regression. The correlation between naive/memory T cells and tumor progression was investigated by Student’s t test. Results: CD4+ naive/memory ratio showed close correlations with hemoglobin, red blood cell (RBC), absolute neutrophil count (ANC) and platelet while CD8+ naive/memory ratio was correlated with hemoglobin, RBC and CEA. Higher baseline lever of CD4+CD45RO+/CD4+ was correlated with better overall survival (OS) (P = 0.036). Patients with CD4+ naive/memory ratio ≥ 0.36 had a poorer OS than those with CD4+ naive/memory ratio < 0.36 (P = 0.021). In addition, CD4+ naive/memory ratio showed independent prognostic impact (HR 1.427, 95%CI 1.033-1.973, P = 0.031). Furthermore, poorer clinical response was correlated with higher level of CD8+ naive/memory ratio after the third cycle of chemotherapy (P = 0.01). Besides, patients with an low level of CD8+ naive/memory ratio had longer progression-free survival (PFS) (P = 0.028). Conclusions: We propose CD4+ naive/memory ratio as a novel prognostic biomarker for APC. In addition, CD8+ naive/memory ratio can be a candidate marker for predicting PFS and the change of its level may reflect the progression of APC.
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Steffens, Carolyn M., Elizabeth Z. Managlia, Alan Landay, and Lena Al-Harthi. "Interleukin-7–treated naive T cells can be productively infected by T-cell–adapted and primary isolates of human immunodeficiency virus 1." Blood 99, no. 9 (May 1, 2002): 3310–18. http://dx.doi.org/10.1182/blood.v99.9.3310.

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Abstract Although human immunodeficiency virus (HIV)gag/pol DNA can be detected in naive T cells, whether naive T cells can be productively infected by HIV is still questionable. Given that interleukin-7 (IL-7) is a prospective therapeutic immunomodulator for the treatment of HIV, we evaluated the effect of IL-7 on promoting naive T-cell infection of laboratory-adapted (IIIB), M-tropic, and primary isolates of HIV. Initially, we determined that the 3 cell surface markers widely used to identify naive T cells (CD45RA+CD45RO−, CD45RA+CD62L+, and CD45RO−CD27+CD95low) are all equivalent in T-cell receptor excision circle content, a marker for the replicative history of a cell as well as for de novo T cells. We therefore used CD45RA+CD45RO− expression to define naive T cells in this study. We demonstrate that although untreated or IL-2–treated naive T cells are not productively infected by HIV, IL-7 pretreatment mediated the productive infection of laboratory-adapted, M-tropic, and primary isolates of HIV as determined by p24 core antigen production. This up-regulation was between 8- and 58-fold, depending on the HIV isolate used. IL-7 pretreatment of naive T cells also potently up-regulated surface expression of CXCR4 but not CCR5 and mediated the expansion of naive T cells without the acquisition of the primed CD45RO phenotype. Collectively, these data indicate that IL-7 augments naive T-cell susceptibility to HIV and that under the appropriate environmental milieu, naive T cells may be a source of HIV productive infection. This information needs to be considered in evaluating IL-7 as an immunomodulator for HIV-infected patients.
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25

Goldrath, Ananda W., Lisa Y. Bogatzki, and Michael J. Bevan. "Naive T Cells Transiently Acquire a Memory-like Phenotype during Homeostasis-Driven Proliferation." Journal of Experimental Medicine 192, no. 4 (August 21, 2000): 557–64. http://dx.doi.org/10.1084/jem.192.4.557.

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In a depleted lymphoid compartment, naive T cells begin a slow proliferation that is independent of cognate antigen yet requires recognition of major histocompatibility complex–bound self-peptides. We have followed the phenotypic and functional changes that occur when naive CD8+ T cells undergo this type of expansion in a lymphopenic environment. Naive T cells undergoing homeostasis-driven proliferation convert to a phenotypic and functional state similar to that of memory T cells, yet distinct from antigen-activated effector T cells. Naive T cells dividing in a lymphopenic host upregulate CD44, CD122 (interleukin 2 receptor β) and Ly6C expression, acquire the ability to rapidly secrete interferon γ, and become cytotoxic effectors when stimulated with cognate antigen. The conversion of naive T cells to cells masquerading as memory cells in response to a homeostatic signal does not represent an irreversible differentiation. Once the cellularity of the lymphoid compartment is restored and the T cells cease their division, they regain the functional and phenotypic characteristics of naive T cells. Thus, homeostasis-driven proliferation provides a thymus-independent mechanism for restoration of the naive compartment after a loss of T cells.
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26

Ostrowski, Mario A., Tae-Wook Chun, Shawn J. Justement, Ivette Motola, Michael A. Spinelli, Joseph Adelsberger, Linda A. Ehler, Stephanie B. Mizell, Claire W. Hallahan, and Anthony S. Fauci. "Both Memory and CD45RA+/CD62L+ Naive CD4+ T Cells Are Infected in Human Immunodeficiency Virus Type 1-Infected Individuals." Journal of Virology 73, no. 8 (August 1, 1999): 6430–35. http://dx.doi.org/10.1128/jvi.73.8.6430-6435.1999.

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ABSTRACT Cellular activation is critical for the propagation of human immunodeficiency virus type 1 (HIV-1) infection. It has been suggested that truly naive CD4+ T cells are resistant to productive HIV-1 infection because of their constitutive resting state. Memory and naive CD4+ T-cell subsets from 11 HIV-1-infected individuals were isolated ex vivo by a combination of magnetic bead depletion and fluorescence-activated cell sorting techniques with stringent criteria of combined expression of CD45RA and CD62L to identify naive CD4+ T-cell subsets. In all patients HIV-1 provirus could be detected within naive CD45RA+/CD62L+ CD4+ T cells; in addition, replication-competent HIV-1 was isolated from these cells upon CD4+ T-cell stimulation in tissue cultures. Memory CD4+ T cells had a median of fourfold more replication-competent virus and a median of sixfold more provirus than naive CD4+ T cells. Overall, there was a median of 16-fold more integrated provirus identified in memory CD4+ T cells than in naive CD4+ T cells within a given patient. Interestingly, there was a trend toward equalization of viral loads in memory and naive CD4+ T-cell subsets in those patients who harbored CXCR4-using (syncytium-inducing) viruses. Within any given patient, there was no selective usage of a particular coreceptor by virus isolated from memory versus naive CD4+ T cells. Our findings suggest that naive CD4+ T cells may be a significant viral reservoir for HIV, particularly in those patients harboring CXCR4-using viruses.
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27

Saalmüller, Armin, Tobias Werner, and Vicky Fachinger. "T-helper cells from naive to committed." Veterinary Immunology and Immunopathology 87, no. 3-4 (September 2002): 137–45. http://dx.doi.org/10.1016/s0165-2427(02)00045-4.

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28

Oppenheimer-Marks, Nancy, and Peter E. Lipsky. "Migration of naive and memory T cells." Immunology Today 18, no. 9 (September 1997): 456–57. http://dx.doi.org/10.1016/s0167-5699(97)82723-5.

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29

Komanduri, Krishna V. "A maturing understanding of naive T cells." Blood 125, no. 18 (April 30, 2015): 2742–43. http://dx.doi.org/10.1182/blood-2015-03-633636.

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30

Surh, Charles D., and Jonathan Sprent. "Homeostasis of Naive and Memory T Cells." Immunity 29, no. 6 (December 2008): 848–62. http://dx.doi.org/10.1016/j.immuni.2008.11.002.

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31

Kawabe, Takeshi, Jaeu Yi, and Jonathan Sprent. "Homeostasis of Naive and Memory T Lymphocytes." Cold Spring Harbor Perspectives in Biology 13, no. 9 (March 22, 2021): a037879. http://dx.doi.org/10.1101/cshperspect.a037879.

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32

Cicin-Sain, L., I. Messaoudi, B. Park, N. Currier, S. Planer, M. Fischer, S. Tackitt, et al. "Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates." Proceedings of the National Academy of Sciences 104, no. 50 (December 4, 2007): 19960–65. http://dx.doi.org/10.1073/pnas.0705905104.

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33

Cho, Bryan K., Varada P. Rao, Qing Ge, Herman N. Eisen, and Jianzhu Chen. "Homeostasis-Stimulated Proliferation Drives Naive T Cells to Differentiate Directly into Memory T Cells." Journal of Experimental Medicine 192, no. 4 (August 21, 2000): 549–56. http://dx.doi.org/10.1084/jem.192.4.549.

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The developmental requirements for immunological memory, a central feature of adaptive immune responses, is largely obscure. We show that as naive CD8 T cells undergo homeostasis-driven proliferation in lymphopenic mice in the absence of overt antigenic stimulation, they progressively acquire phenotypic and functional characteristics of antigen-induced memory CD8 T cells. Thus, the homeostasis-induced memory CD8 T cells express typical memory cell markers, lyse target cells directly in vitro and in vivo, respond to lower doses of antigen than naive cells, and secrete interferon γ faster upon restimulation. Like antigen-induced memory T cell differentiation, the homeostasis-driven process requires T cell proliferation and, initially, the presence of appropriate restricting major histocompatibility complexes, but it differs by occurring without effector cell formation and without requiring interleukin 2 or costimulation via CD28. These findings define repetitive cell division plus T cell receptor ligation as the basic requirements for naive to memory T cell differentiation.
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34

Cekic, Caglar, Duygu Sag, Yuan-Ji Day, and Joel Linden. "Extracellular adenosine regulates naive T cell development and peripheral maintenance." Journal of Experimental Medicine 210, no. 12 (October 21, 2013): 2693–706. http://dx.doi.org/10.1084/jem.20130249.

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Adenosine produced as a byproduct of metabolic activity is present in all tissues and produces dose-dependent suppression of TCR signaling. Naive T cell maintenance depends on inhibition of TCR signals by environmental sensors, which are yet to be fully defined. We produced mice with a floxed adenosine A2A receptor (A2AR) gene, Adora2a, and show that either global A2AR deletion or cre-mediated T cell deletion elicits a decline in the number of naive but not memory T cells. A2AR signaling maintains naive T cells in a quiescent state by inhibiting TCR-induced activation of the phosphatidylinositide 3-kinase (PI3K)–AKT pathway, thereby reducing IL-7Rα down-regulation and naive T cell apoptosis. Patterns of IL-7Rα expression on T cells in chimeric mice reconstituted with Adora2a+/+ and Adora2a−/− bone marrow cells suggest that decreased IL-7Rα in naive T cells is a cell-intrinsic consequence of Adora2a deletion. In addition, A2AR expression increases in early thymic T cell development and contributes to progression of double-negative thymic precursors to single-positive thymocytes with increased IL-7Rα expression. Therefore, A2AR signaling regulates T cell development and maintenance to sustain normal numbers of naive T cells in the periphery.
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35

Kohler, Siegfried, and Andreas Thiel. "Life after the thymus: CD31+ and CD31− human naive CD4+ T-cell subsets." Blood 113, no. 4 (January 22, 2009): 769–74. http://dx.doi.org/10.1182/blood-2008-02-139154.

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Abstract Early in life, thymic export establishes the size and the diversity of the human naive T-cell pool. Yet, on puberty thymic activity drastically decreases. Because the overall size of the naive T-cell pool decreases only marginally during ageing, peripheral postthymic expansion of naive T cells has been postulated to account partly for the maintenance of T-cell immunity in adults. So far, the analysis of these processes had been hampered by the inability to distinguish recent thymic emigrants from proliferated, peripheral, naive T cells. However, recently, CD31 has been introduced as a marker to distinguish 2 subsets of naive CD4+ T cells with distinct T-cell receptor excision circle (TREC) content in the peripheral blood of healthy humans. Here, we review studies that have characterized TREChi CD31+ thymicnaive CD4+ T cells and have accordingly used the assessment of this distinct subset of naive CD4+ T cells as a correlate of thymic activity. We will discuss further potential clinical applications and how more research on CD31+ thymicnaive and CD31− centralnaive CD4+ T cells may foster our knowledge of the impact of thymic involution on immune competence.
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36

Richards, Stephen J., Gareth J. Morgan, and Peter Hillmen. "Analysis of T Cells in Paroxysmal Nocturnal Hemoglobinuria Provides Direct Evidence That Thymic T-Cell Production Declines With Age." Blood 94, no. 8 (October 15, 1999): 2790–99. http://dx.doi.org/10.1182/blood.v94.8.2790.420k08_2790_2799.

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Peripheral blood T cells in patients with paroxysmal nocturnal hemoglobinuria (PNH) comprise a mixture of residual normal and glycosylphosphatidylinositol (GPI)-deficient PNH cells. Using multicolor flow cytometry, we demonstrated significant differences between the proportions of naive and memory cells within these populations. PNH T cells comprise mainly naive cells (CD45RA+CD45R0−), whereas normal T cells in the same patients were predominantly memory (CD45RA−CD45R0+) cells. Functional analyses showed that GPI-deficient CD45RA+ T cells can convert to a CD45R0+ phenotype. We present data from a PNH patient in remission for 20 years who still had significant numbers of GPI-deficient T cells; these showed a normal distribution of naive and memory components. The predominantly naive phenotype of GPI-deficient T cells seen in PNH patients with active disease likely reflects the phenotype of recent normal thymic emigrants. In patients where hematopoiesis was predominantly derived from the PNH stem cell, absolute numbers of both naive PNH CD4+ cells and CD8+ cells show an inverse correlation with patient age, implying this age-related decline in T-cell production is secondary to a decrease in thymic activity rather than a stem cell defect.
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37

Dion, Marie-Lise, Rebeka Bordi, Joumana Zeidan, Robert Asaad, Mohammed-Rachid Boulassel, Jean-Pierre Routy, Micheal M. Lederman, Rafick-Pierre Sekaly, and Remi Cheynier. "Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection." Blood 109, no. 7 (December 12, 2006): 2912–20. http://dx.doi.org/10.1182/blood-2006-09-047308.

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AbstractIn chronic HIV infection, most untreated patients lose naive CD4+ and CD8+ T cells, whereas a minority preserve them despite persistent high viremia. Although antiretroviral therapy (ART)–mediated viral suppression generally results in a rise of naive and total CD4+ T cells, certain patients experience very little or no T-cell reconstitution. High peripheral T-cell activation has been linked to poor clinical outcomes, interfering with previous evaluations of thymic function in disease progression and therapy-mediated T-cell recovery. To circumvent this, we used the sj/βTREC ratio, a robust index of thymopoiesis that is independent of peripheral T-cell proliferation, to evaluate the thymic contribution to the preservation and restoration of naive CD4+ T cells. We show that the loss of naive and total CD4+ T cells is the result of or is exacerbated by a sustained thymic defect, whereas efficient thymopoiesis supports naive and total CD4+ T-cell maintenance in slow progressor patients. In ART-treated patients, CD4+ T-cell recovery was associated with the normalization of thymopoiesis, whereas the thymic defect persisted in aviremic patients who failed to recover CD4+ T-cell counts. Overall, we demonstrate that efficient thymopoiesis is key in the natural maintenance and in therapy-mediated recovery of naive and total CD4+ T cells.
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38

Brehm, Michael A., Julie Mangada, Thomas G. Markees, Todd Pearson, Keith A. Daniels, Thomas B. Thornley, Raymond M. Welsh, Aldo A. Rossini, and Dale L. Greiner. "Rapid quantification of naive alloreactive T cells by TNF-α production and correlation with allograft rejection in mice." Blood 109, no. 2 (September 14, 2006): 819–26. http://dx.doi.org/10.1182/blood-2006-03-008219.

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Abstract Allograft transplantation requires chronic immunosuppression, but there is no effective strategy to evaluate the long-term maintenance of immunosuppression other than assessment of graft function. The ability to monitor naive alloreactive T cells would provide an alternative guide for drug therapy at early, preclinical stages of graft rejection and for evaluating tolerance-inducing protocols. To detect and quantify naive alloreactive T cells directly ex vivo, we used the unique ability of naive T cells to rapidly produce TNF-α but not IFN-γ. Naive alloreactive T cells were identified by the production of TNF-α after a 5-hour in vitro stimulation with alloantigen and were distinguished from effector/memory alloreactive T cells by the inability to produce IFN-γ. Moreover, naive alloreactive T cells were not detected in mice tolerized against specific alloantigens. The frequency of TNF-α–producing cells was predictive for rejection in an in vivo cytotoxicity assay and correlated with skin allograft rejection. Naive alloreactive T cells were also detected in humans, suggesting clinical relevance. We conclude that rapid production of TNF-α can be used to quantify naive alloreactive T cells, that it is abrogated after the induction of tolerance, and that it is a potential tool to predict allograft rejection.
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39

Carson, Monica J., J. Gregor Sutcliffe, and Iain L. Campbell. "Microglia stimulate naive T-cell differentiation without stimulating T-cell proliferation." Journal of Neuroscience Research 55, no. 1 (January 1, 1999): 127–34. http://dx.doi.org/10.1002/(sici)1097-4547(19990101)55:1<127::aid-jnr14>3.0.co;2-2.

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40

Kassiotis, George, Rose Zamoyska, and Brigitta Stockinger. "Involvement of Avidity for Major Histocompatibility Complex in Homeostasis of Naive and Memory T Cells." Journal of Experimental Medicine 197, no. 8 (April 21, 2003): 1007–16. http://dx.doi.org/10.1084/jem.20021812.

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The requirements for survival and self-renewal of peripheral T cells and the nature of mechanisms controlling the size of the naive and memory pool are not completely understood. Here, we examine the involvement of the major histocompatibility complex (MHC) in survival and homeostatic expansion of naive and memory T cells. We show that the homeostatic behavior of naive T cell receptor (TCR)-transgenic T cells can be deduced by the expression levels of TCR and CD5, a negative regulator of TCR signaling. Both these factors determine the strength of TCR stimulation by MHC-derived signals. We further show that, similarly to naive T cells, MHC-derived signals influence the homeostatic expansion capacity of memory T cells under lymphopenic conditions. In contrast to naive T cells, however, memory T cells can reach a homeostatic equilibrium, in which survival/self-renewal of each clone is dissociated from their avidity for MHC-derived signals.
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41

Glinos, Dafni A., Blagoje Soskic, Cayman Williams, Alan Kennedy, Luke Jostins, David M. Sansom, and Gosia Trynka. "Genomic profiling of T-cell activation suggests increased sensitivity of memory T cells to CD28 costimulation." Genes & Immunity 21, no. 6-8 (November 23, 2020): 390–408. http://dx.doi.org/10.1038/s41435-020-00118-0.

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AbstractT-cell activation is a critical driver of immune responses. The CD28 costimulation is an essential regulator of CD4 T-cell responses, however, its relative importance in naive and memory T cells is not fully understood. Using different model systems, we observe that human memory T cells are more sensitive to CD28 costimulation than naive T cells. To deconvolute how the T-cell receptor (TCR) and CD28 orchestrate activation of human T cells, we stimulate cells using varying intensities of TCR and CD28 and profiled gene expression. We show that genes involved in cell cycle progression and division are CD28-driven in memory cells, but under TCR control in naive cells. We further demonstrate that T-helper differentiation and cytokine expression are controlled by CD28. Using chromatin accessibility profiling, we observe that AP1 transcriptional regulation is enriched when both TCR and CD28 are engaged, whereas open chromatin near CD28-sensitive genes is enriched for NF-kB motifs. Lastly, we show that CD28-sensitive genes are enriched in GWAS regions associated with immune diseases, implicating a role for CD28 in disease development. Our study provides important insights into the differential role of costimulation in naive and memory T-cell responses and disease susceptibility.
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42

Takada, Kensuke, and Stephen C. Jameson. "Self–class I MHC molecules support survival of naive CD8 T cells, but depress their functional sensitivity through regulation of CD8 expression levels." Journal of Experimental Medicine 206, no. 10 (September 14, 2009): 2253–69. http://dx.doi.org/10.1084/jem.20082553.

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Previous studies have suggested that naive CD8 T cells require self-peptide–major histocompatability complex (MHC) complexes for maintenance. However, interpretation of such studies is complicated because of the involvement of lymphopenic animals, as lymphopenia drastically alters naive T cell homeostasis and function. In this study, we explored naive CD8 T cell survival and function in nonlymphopenic conditions by using bone marrow chimeric donors and hosts in which class I MHC expression is absent or limited to radiosensitive versus radioresistant cells. We found that long-term survival of naive CD8 T cells (but not CD4 T cells) was impaired in the absence of class I MHC. However, distinct from this effect, class I MHC deprivation also enhanced naive CD8 T cell responsiveness to low-affinity (but not high-affinity) peptide–MHC ligands. We found that this improved sensitivity was a consequence of up-regulated CD8 levels, which was mediated through a transcriptional mechanism. Hence, our data suggest that, in a nonlymphopenic setting, self-class I MHC molecules support CD8 T cell survival, but that these interactions also attenuate naive T cell sensitivity by dynamic tuning of CD8 levels.
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43

Bains, Iren, Rustom Antia, Robin Callard, and Andrew J. Yates. "Quantifying the development of the peripheral naive CD4+ T-cell pool in humans." Blood 113, no. 22 (May 28, 2009): 5480–87. http://dx.doi.org/10.1182/blood-2008-10-184184.

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What are the rules that govern a naive T cell's prospects for survival or division after export from the thymus into the periphery? To help address these questions, we combine data from existing studies with robust mathematical models to estimate the absolute contributions of thymopoiesis, peripheral division, and loss or differentiation to the human naive CD4+ T-cell pool between the ages of 0 and 20 years. Despite their decline in frequency in the blood, total body numbers of naive CD4+ T cells increase throughout childhood and early adulthood. Our analysis shows that postthymic proliferation contributes more than double the number of cells entering the pool each day from the thymus. This ratio is preserved with age; as the thymus involutes, the average time between naive T-cell divisions in the periphery lengthens. We also show that the expected residence time of naive T cells increases with time. The naive CD4+ T-cell population thus becomes progressively less dynamic with age. Together with other studies, our results suggest a complex picture of naive T-cell homeostasis in which population size, time since export from the thymus, or time since the last division can influence a cell's prospects for survival or further divisions.
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44

Mangare, Caroline, Sabine Tischer-Zimmermann, Sebastian B. Riese, Anna C. Dragon, Immo Prinz, Rainer Blasczyk, Britta Maecker-Kolhoff, and Britta Eiz-Vesper. "Robust Identification of Suitable T-Cell Subsets for Personalized CMV-Specific T-Cell Immunotherapy Using CD45RA and CD62L Microbeads." International Journal of Molecular Sciences 20, no. 6 (March 20, 2019): 1415. http://dx.doi.org/10.3390/ijms20061415.

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Viral infections and reactivations remain a serious obstacle to successful hematopoietic stem cell transplantation (HSCT). When antiviral drug treatment fails, adoptive virus-specific T-cell transfer provides an effective alternative. Assuming that naive T cells (TN) are mainly responsible for GvHD, methods were developed to generate naive T-cell-depleted products while preserving immune memory against viral infections. We compared two major strategies to deplete potentially alloreactive T cells: CD45RA and CD62L depletion and analyzed phenotype and functionality of the resulting CD45RA−/CD62L− naive T-cell-depleted as well as CD45RA+/CD62L+ naive T-cell-enriched fractions in the CMV pp65 and IE1 antigen model. CD45RA depletion resulted in loss of terminally differentiated effector memory T cells re-expressing CD45RA (TEMRA), and CD62L depletion in loss of central memory T cells (TCM). Based on these differences in target cell-dependent and target cell-independent assays, antigen-specific T-cell responses in CD62L-depleted fraction were consistently 3–5 fold higher than those in CD45RA-depleted fraction. Interestingly, we also observed high donor variability in the CD45RA-depleted fraction, resulting in a substantial loss of immune memory. Accordingly, we identified donors with expected response (DER) and unexpected response (DUR). Taken together, our results showed that a naive T-cell depletion method should be chosen individually, based on the immunophenotypic composition of the T-cell populations present.
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45

O'MALLEY, ROBERT E. "NAIVE SINGULAR PERTURBATION THEORY." Mathematical Models and Methods in Applied Sciences 11, no. 01 (February 2001): 119–31. http://dx.doi.org/10.1142/s0218202501000787.

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The paper demonstrates, via extremely simple examples, the shocks, spikes, and initial layers that arise in solving certain singularly perturbed initial value problems for first-order ordinary differential equations. As examples from stability theory, they are basic to many asymptotic techniques. First, we note that limiting solutions of linear homogeneous equations [Formula: see text] on t≥0 are specified by the zeros of [Formula: see text], rather than by the turning points where a(t) becomes zero. Furthermore, solutions to the solvable equations [Formula: see text] for k=1, 2 or 3 can feature canards, where the trivial limit continues to apply after it becomes repulsive. Limiting solutions of the separable equation [Formula: see text] may likewise involve switchings between the zeros of c(x) located immediately above and below x(0), if they exist, at zeros of A(t). Finally, limiting solutions of many other problems follow by using asymptotic expansions for appropriate special functions. For example, solutions of [Formula: see text] can be given in terms of the Bessel functions Kj(t4/4ε) and Ij(t4/4ε) for j=3/8 and -5/8.
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46

Favre, David, Cheryl A. Stoddart, Brinda Emu, Rebecca Hoh, Jeffrey N. Martin, Frederick M. Hecht, Steven G. Deeks, and Joseph M. McCune. "HIV disease progression correlates with the generation of dysfunctional naive CD8low T cells." Blood 117, no. 7 (February 17, 2011): 2189–99. http://dx.doi.org/10.1182/blood-2010-06-288035.

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Abstract HIV infection can result in depletion of total CD4+ T cells and naive CD8+ T cells, and in the generation of dysfunctional effector CD8+ T cells. In this study, we show that naive CD8+ T cells in subjects with progressive HIV disease express low levels of CD8α and CD8β chains. Such naive CD8low T cells display broad signaling defects across the T-cell receptor complex, and their appearance correlates with generalized up-regulation of major histocompatibility complex class I (MHC-I) antigens on peripheral blood mononuclear cells (PBMCs). To explore a causal link between increased MHC-I up-regulation and the generation of naive CD8low T cells, we used the humanized SCID-hu Thy/Liv mouse model to show that HIV infection of the thymus and interferon α (IFNα) treatment alone result in MHC-I up-regulation and in the generation of dysfunctional CD3highCD8+CD4− single-positive 8 (SP8) thymocytes with low expression of CD8. We suggest that dysfunctional naive CD8low T cells are generated as a result of IFNα-mediated up-regulation of MHC-I on stromal cells in the thymus and antigen-presenting cells in the periphery, and that dysfunction in this naive compartment contributes to the immunodeficiency of HIV disease. This study is registered at www.clinicaltrials.gov as NCT00187512.
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47

Kanegane, H., and G. Tosato. "Activation of naive and memory T cells by interleukin-15." Blood 88, no. 1 (July 1, 1996): 230–35. http://dx.doi.org/10.1182/blood.v88.1.230.230.

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Abstract Interleukin-15 (IL-15), a product of monocytes and other cells, has biological activities similar to those of IL-2, including growth stimulation of activated T cells, induction of cytolytic effector cells, and B-cell costimulation for proliferation and lg production. We report that IL-15 at optimal concentrations rapidly induced memory (CD45RO+) CD4+ and CD8+ T cells and naive (CD45RO-) CD8+ T cells to express the CD69 activation marker followed by proliferation. By contrast, IL-15 failed to induce naive (CD45RO-) CD4+ T cells to express CD69 or to proliferate. Similar findings were obtained with IL- 2. Unlike the other T-cell subsets, CD4+ T cells with a naive phenotype expressed little or no IL-2R beta chain, a shared component of the IL-2 and IL-15 receptors required for receptor function. A monoclonal antibody to the IL-2R beta chain, Mik beta 1, reduced CD69 expression and proliferation in CD4+ memory, CD8+ memory, and CD8+ naive T cells activated by IL-15. These results confirm the biological similarities of IL-2 and IL-15. They further document that the pool of naive CD4+ cells, unlike the pool of memory CD4+, memory CD8+, and naive CD8+ cells, is not regulated directly by the T-cell growth factors IL-2 or IL-15.
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48

Kanegane, H., and G. Tosato. "Activation of naive and memory T cells by interleukin-15." Blood 88, no. 1 (July 1, 1996): 230–35. http://dx.doi.org/10.1182/blood.v88.1.230.bloodjournal881230.

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Interleukin-15 (IL-15), a product of monocytes and other cells, has biological activities similar to those of IL-2, including growth stimulation of activated T cells, induction of cytolytic effector cells, and B-cell costimulation for proliferation and lg production. We report that IL-15 at optimal concentrations rapidly induced memory (CD45RO+) CD4+ and CD8+ T cells and naive (CD45RO-) CD8+ T cells to express the CD69 activation marker followed by proliferation. By contrast, IL-15 failed to induce naive (CD45RO-) CD4+ T cells to express CD69 or to proliferate. Similar findings were obtained with IL- 2. Unlike the other T-cell subsets, CD4+ T cells with a naive phenotype expressed little or no IL-2R beta chain, a shared component of the IL-2 and IL-15 receptors required for receptor function. A monoclonal antibody to the IL-2R beta chain, Mik beta 1, reduced CD69 expression and proliferation in CD4+ memory, CD8+ memory, and CD8+ naive T cells activated by IL-15. These results confirm the biological similarities of IL-2 and IL-15. They further document that the pool of naive CD4+ cells, unlike the pool of memory CD4+, memory CD8+, and naive CD8+ cells, is not regulated directly by the T-cell growth factors IL-2 or IL-15.
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49

Cassell, D. J., and R. H. Schwartz. "A quantitative analysis of antigen-presenting cell function: activated B cells stimulate naive CD4 T cells but are inferior to dendritic cells in providing costimulation." Journal of Experimental Medicine 180, no. 5 (November 1, 1994): 1829–40. http://dx.doi.org/10.1084/jem.180.5.1829.

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Ligation of CD28 on CD4 Th1 clones and freshly isolated mixtures of naive and memory CD4 T cells triggered their T cell receptors (TCR) is sufficient to induce the costimulatory signals necessary for interleukin 2 (IL-2) production by these cells. CTLA-4-reactive ligands expressed on antigen-presenting cells (APC) are critical in providing costimulatory signals to these T cell populations. We demonstrate that these activation characteristics apply equally to purified naive CD4 T cells. Because B cell blasts express CTLA-4-reactive ligands and high levels of adhesion and major histocompatibility complex class II molecules, they would be expected to engage both the TCR and CD28 and consequently stimulate IL-2 production by naive CD4 T cells. Using purified populations of cells in limiting dilution cultures, we have carried out a quantitative analysis of the interaction between naive CD4 T cells and either activated B or dendritic cells. We demonstrate that B cell blasts stimulate a high frequency of naive CD4 T cells. Slight differences in TCR signaling efficiency between the two APC types were observed. Even at optimal peptide concentrations, however, the amount of IL-2 made by individual T cells was fourfold lower in response to B cell blasts than to dendritic cells. This relative deficiency of activated B cells was due to their inability to optimally costimulate naive CD4 T cells.
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50

Wojciechowski, Sara, Pulak Tripathi, Tristan Bourdeau, Luis Acero, H. Leighton Grimes, Jonathan D. Katz, Fred D. Finkelman, and David A. Hildeman. "Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis." Journal of Experimental Medicine 204, no. 7 (June 25, 2007): 1665–75. http://dx.doi.org/10.1084/jem.20070618.

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We examined the role of the antiapoptotic molecule Bcl-2 in combating the proapoptotic molecule Bim in control of naive and memory T cell homeostasis using Bcl-2−/− mice that were additionally deficient in one or both alleles of Bim. Naive T cells were significantly decreased in Bim+/−Bcl-2−/− mice, but were largely restored in Bim−/−Bcl-2−/− mice. Similarly, a synthetic Bcl-2 inhibitor killed wild-type, but not Bim−/−, T cells. Further, T cells from Bim+/−Bcl-2−/− mice died rapidly ex vivo and were refractory to cytokine-driven survival in vitro. In vivo, naive CD8+ T cells required Bcl-2 to combat Bim to maintain peripheral survival, whereas naive CD4+ T cells did not. In contrast, Bim+/−Bcl-2−/− mice generated relatively normal numbers of memory T cells after lymphocytic choriomeningitis virus infection. Accumulation of memory T cells in Bim+/−Bcl-2−/− mice was likely caused by their increased proliferative renewal because of the lymphopenic environment of the mice. Collectively, these data demonstrate a critical role for a balance between Bim and Bcl-2 in controlling homeostasis of naive and memory T cells.
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