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Journal articles on the topic 'CD8+ Treg cells'

Author: Grafiati

Published: 3 June 2025

Last updated: 31 July 2025

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1

Panda, Abir Kumar, and Ethan M. Shevach. "CD28 co-stimulation drives memory phenotype (MP) Treg cell and MP CD4+Foxp3− effector T cell homeostatic proliferation." Journal of Immunology 200, no. 1_Supplement (2018): 112.11. http://dx.doi.org/10.4049/jimmunol.200.supp.112.11.

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Abstract Foxp3+Tregs, CD4+Foxp3− effector T cells and CD8+ T cells are composed of naïve (NP, CD44loCD62Lhi) and memory (MP, CD44hiCD62Llo) subsets. About 30% of MP T cells are cycling (Ki-67+) in-vivo. To determine the factors that drive T cell homeostatic proliferation in-vivo, we investigated the roles of cytokines (TNFa, IL-2, IL-7, and IL-33), TCR-MHC-II interactions, co-stimulatory (CD28, ICOS, CD40, GITR, OX40), and co-inhibitory (CTLA-4, PD1, BTLA, TIGIT) receptors. Blockade of CD28-CD80/86 signaling completely inhibited MP Treg and MP CD4+Foxp3− effector T cell proliferation but did n

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Ceeraz, Sabrina, Charlotte R. Thompson, Richard Beatson, and Ernest H. Choy. "Harnessing CD8+CD28− Regulatory T Cells as a Tool to Treat Autoimmune Disease." Cells 10, no. 11 (2021): 2973. http://dx.doi.org/10.3390/cells10112973.

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T regulatory cell therapy presents a novel therapeutic strategy for patients with autoimmune diseases or who are undergoing transplantation. At present, the CD4+ Treg population has been extensively characterized, as a result of defined phenotypic and functional readouts. In this review article, we discuss the development and biology of CD8+ Tregs and their role in murine and human disease indications. A subset of CD8+ Tregs that lack the surface expression of CD28 (CD8+CD28− Treg) has proved efficacious in preclinical models. CD8+CD28− Tregs are present in healthy individuals, but their impai

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Gardell, Jennifer L., Courtney Crane, Justin Bowser, et al. "Bispecific CD8 Treg modulators regulate a novel regulatory CD8 T cell network and eliminate pathogenic CD4 T cells in live cell co-culture system." Journal of Immunology 208, no. 1_Supplement (2022): 174.16. http://dx.doi.org/10.4049/jimmunol.208.supp.174.16.

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Abstract INTRODUCTION Others have described a subset of CD8 T cells (CD8 Treg) with immunosuppressive characteristics in inflammatory disease settings. CD8 Treg activation through canonical T cell receptors results in their oligoclonal expansion and perforin dependent elimination of pathogenic CD4 T cells. We have described the CD8 Treg network in Celiac patients and its potential to eliminate pathogenic CD4 T cells. Here we describe bispecific CD8 Treg modulators that activate CD8 Tregs, resulting in pathogenic CD4 T cell death. METHODS Novel bispecific CD8 Treg modulators were tested for tar

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Zhang, Zhu Xu, Ye Su, Xuyan Huang, Dameng Lian, and Anthony Jevnikar. "CD4+ but not CD8+ memory T cells escape DN Tregs-mediated regulation via expression of Serpin Protease Inhibitor 6 (P2160)." Journal of Immunology 190, no. 1_Supplement (2013): 69.18. http://dx.doi.org/10.4049/jimmunol.190.supp.69.18.

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Abstract Memory T cell (Tm) homeostasis is poorly understood and is a critical challenge to prevent transplant rejection. At present there are no effective clinical strategies to control Tm and contradictory reports exist as to their control by regulatory T cell (Treg). We previously found that TCRab+CD3+CD4-CD8-NK1.1- (double-negative, DN) Treg could effectively suppress CD4+ and CD8+ effector T cells and thus prevent transplant rejection. We utilized this model to test whether DN Tregs could similarly suppress Tm. Interestingly DN Tregs suppressed CD8+ Tm but had no effect on CD4+ Tm cells.

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Maurer, Meghan, Justin Bowser, Rachael Fasnacht, et al. "Demonstration of regulatory CD8 T cell prevalence, phenotype, and functions in autoimmune patients treated with a tolerizing peptide vaccine." Journal of Immunology 208, no. 1_Supplement (2022): 123.10. http://dx.doi.org/10.4049/jimmunol.208.supp.123.10.

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Abstract INTRODUCTION Others have described a subset of CD8 T cells with immunosuppressive characteristics in inflammatory disease settings. CD8 Treg activation, through a canonical T cell receptor, results in oligoclonal expansion and perforin dependent elimination of pathogenic CD4 T cells. We have demonstrated the CD8 Treg network in Celiac patients, and that CD8 Tregs can be modulated to enhance their cytolytic elimination of pathogenic CD4 T cells. Here, we evaluate culture conditions to enhance CD8 Treg functions, and describe the impact of a gluten tolerizing peptide vaccine on CD8 Treg

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Rushbrook, Simon M., Scott M. Ward, Esther Unitt, et al. "Regulatory T Cells Suppress In Vitro Proliferation of Virus-Specific CD8+ T Cells during Persistent Hepatitis C Virus Infection." Journal of Virology 79, no. 12 (2005): 7852–59. http://dx.doi.org/10.1128/jvi.79.12.7852-7859.2005.

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ABSTRACT The basis of chronic infection following exposure to hepatitis C virus (HCV) infection is unexplained. One factor may be the low frequency and immature phenotype of virus-specific CD8+ T cells. The role of CD4+CD25+ T regulatory (Treg) cells in priming and expanding virus-specific CD8+ T cells was investigated. Twenty HLA-A2-positive patients with persistent HCV infection and 46 healthy controls were studied. Virus-specific CD8+ T-cell proliferation and gamma interferon (IFN-γ) frequency were analyzed with/without depletion of Treg cells, using peptides derived from HCV, Epstein-Barr

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Botta, Gregory P., Tatiana Hurtado De Mendoza, Harri Jarvelainen, and Erkki Ruoslahti. "iRGD in combination with IL-2 reprograms tumor immunosuppression." Journal of Clinical Oncology 37, no. 8_suppl (2019): 55. http://dx.doi.org/10.1200/jco.2019.37.8_suppl.55.

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55 Background: Fibrotic solid tumors have lagged in immunotherapy efficacy. Although breast cancer (BC) shows modest single-agent activity, pancreatic ductal adenocarcinoma (PDAC) immunotherapy has repeatedly failed in clinical trials. A protective desmoplastic, inflammatory reaction encapsulates BC and PDAC where it can make up to 80% of the tumor microenvironment (TME). Reports in BC and PDAC patients and mouse models suggest that tumoricidal effector CD8+ T-cells are indeed present, yet suppressed by regulatory CD4+/CD25+/FoxP3+ T-cells (Tregs) and myeloid cells. Long-term PDAC and BC survi

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Gardell, Jennifer, Daniel Boster, Justin Bowser, et al. "A NOVEL BISPECIFIC CD8 TREG MODULATOR TARGETING CYTOLYTIC CD8 REGULATORY T CELLS REDUCES PATHOGENIC CD4 T CELLS AND INFLAMMATION IN TRANSLATIONAL MODELS OF INTESTINAL AUTOIMMUNE AND INFLAMMATORY DISEASE." Inflammatory Bowel Diseases 29, Supplement_1 (2023): S12. http://dx.doi.org/10.1093/ibd/izac247.024.

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Abstract INTRODUCTION We have characterized a novel CD8 Treg network in autoimmune patient peripheral blood and tissues, in which a subset of cytolytic CD8 Treg eliminate pathogenic CD4 T cells, reducing inflammation and ameliorating disease in response to pathogenic CD4 T cell activation. We hypothesize that the CD8 Treg network is dysfunctional in patients with Celiac and Crohn’s disease, allowing pathogenic CD4 T cell expansion, the initiation of a cascade of inflammatory pathological consequences and the perpetuation of tissue destructive inflammation in Celiac disease and IBD. Here we dem

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Li, Rong, Juan Xu, Ming Wu та ін. "Circulating CD4+ Treg, CD8+ Treg, and CD3+ γδ T Cell Subpopulations in Ovarian Cancer". Medicina 59, № 2 (2023): 205. http://dx.doi.org/10.3390/medicina59020205.

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Background and Objectives: Regulatory T cells (Tregs) are usually enriched in ovarian cancer (OC), and their immunosuppressive function plays a key role in tumorigenesis and progression. We mainly explored the phenotypical characterization of Treg-related markers on αβ and γδ T cell subsets in patients with OC. Materials and Methods: Thirty-six untreated patients with OC at the Women’s Hospital of Nanjing Medical University from September 2019 to August 2021 were enrolled. Phenotypical characterization of Tregs-related markers were detected by flow cytometry (FCM). Enzyme-linked immunosorbent

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Yamagami, Wataru, Nobuyuki Susumu, Hideo Tanaka, et al. "Immunofluorescence-Detected Infiltration of CD4+FOXP3+ Regulatory T Cells is Relevant to the Prognosis of Patients With Endometrial Cancer." International Journal of Gynecologic Cancer 21, no. 9 (2011): 1628–34. http://dx.doi.org/10.1097/igc.0b013e31822c271f.

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ObjectiveHost antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8+ cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients.MethodsThe study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospit

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Yuan, Shiwen, Yanting Zeng, Jiawei Li, et al. "Phenotypical changes and clinical significance of CD4⁺/CD8⁺ T cells in SLE." Lupus Science & Medicine 9, no. 1 (2022): e000660. http://dx.doi.org/10.1136/lupus-2022-000660.

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ObjectiveT cells display significant phenotypical changes and play multiple roles in promoting the immune response in SLE. The frequencies of T cell subpopulations in SLE are still not well understood. To better understanding the phenotypic abnormalities of T cells in SLE will help us to clarify disease immunopathology and to find promising biomarkers for disease monitoring and control.MethodsPeripheral blood CD4+ and CD8+ T cells and their subsets were determined by flow cytometry. Forty-one active SLE patients were selected, including 28 new-onset patients and 13 relapsing patients. One hund

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Panda, Abir Kumar, and Ethan M. Shevach. "Inhibition of TCR-MHC-II interactions abrogates Treg-mediated immune suppression and augments anti-tumor immunity." Journal of Immunology 210, no. 1_Supplement (2023): 169.15. http://dx.doi.org/10.4049/jimmunol.210.supp.169.15.

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Abstract CD4 +Foxp3 +Tregs play a non-redundant role in controlling autoimmunity. Continuous TCR signaling and the availability of exogenous IL-2 from CD4 +effectors regulate the size of the Treg pool and their suppressive function in the steady state. Homeostatic proliferation of Tregs and memory phenotype (MP) CD4 +Foxp3 −T cells depends on CD80/CD86-CD28 signaling. Acute blockade of TCR-MHC-II interactions in vivo by anti-MHC-II mAb significantly enhances memory phenotype (MP) Treg, CD4 +, and CD8 +T cell expansion by a CD28-dependent pathway. IL-15 trans presentation by APC also contribute

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Houston, Timothy W., Quentin Howlett-Prieto, Colin Regenauer, et al. "Increased Percentage of CD8⁺CD28⁻Regulatory T Cells With Fingolimod Therapy in Multiple Sclerosis." Neurology - Neuroimmunology Neuroinflammation 10, no. 2 (2022): e200075. http://dx.doi.org/10.1212/nxi.0000000000200075.

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Background and ObjectivesFingolimod, an oral therapy for MS, decreases expression of membrane S1P1 receptors on CD4+memory cells, causing their retention and deactivation in lymph nodes. We determined fingolimod effects on the number and proportion of potentially CNS-damaging CD8+CD28+cytolytic T lymphocyte cells (CTLs) and on MS-depleted and dysfunctional CD8+CD28−anti-inflammatory suppressor/regulatory T cells (Treg) and on CD8+T-cell expression of the CD69 activation/lymph node retention protein in MS.MethodsCD8, CD28, CD4, and CD69 expression on peripheral blood mononuclear cells was measu

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Mansoori, Mohammad Nizam, Olena Kamenyeva, Juraj Kabat, and Ethan M. Shevach. "Tregs suppress antigen-specific CD8+ T cells in vivo by depleting pMHC-I complexes from Dendritic Cells." Journal of Immunology 208, no. 1_Supplement (2022): 54.10. http://dx.doi.org/10.4049/jimmunol.208.supp.54.10.

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Abstract T Regulatory cells (Tregs) regulate antigen-specific immune responses by using a variety of mechanisms. Recent studies have shown that antigen-specific Treg can suppress CD4+ effector T cells in vitro and in vivo by depleting peptide-MHC-II complexes from the DC surface. It remains unclear as to how Treg suppress CD8+ T effectors, particularly in vivo. To explore Treg-mediated suppression of CD8+ T cells, we generated CD4+ iTregs from OT-II mice specific for Ova323–339 in association with I-Ab and determined their capacity to suppress CD8+ T cells from OT-I mice specific for Ova257–26

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Gupta, Sudhir, Houfen Su, and Sudhanshu Agrawal. "CD8 Treg Cells Inhibit B-Cell Proliferation and Immunoglobulin Production." International Archives of Allergy and Immunology 181, no. 12 (2020): 947–55. http://dx.doi.org/10.1159/000509607.

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<b><i>Aim:</i></b> The role of CD4+ Treg in immune responses has been well established. More recently, a role of CD8+ T regulatory cells (CD8 Treg) in the regulation of immune responses in health and autoimmune diseases has been investigated. Furthermore, different investigators have used different markers to define CD8 Treg. Finally, regulatory effects of CD8 Treg have been studied against T-cell responses; however, their role in regulating B-cell proliferation and immunoglobulin production has not been evaluated. Therefore, in this study we examined the effect of two

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Murase, Kazuyuki, Yutaka Kawano, Jeremy Ryan, et al. "Differential Effects of TCR Stimulation and IL-2 On Apoptotic Pathways in CD4 Regulatory T Cells Compared to Conventional CD4 T Cells and CD8 T Cells." Blood 120, no. 21 (2012): 3280. http://dx.doi.org/10.1182/blood.v120.21.3280.3280.

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Abstract Abstract 3280 CD4+CD25+Foxp3+ regulatory T cells (Treg) play an important role in the maintenance of self-tolerance and immune homeostasis and Treg deficiency contributes to the development of autoimmune diseases. CD4Treg, conventional CD4 T cells (Tcon) and CD8 T cells are derived from lymphocyte progenitor cells that differentiate into distinct functional subsets in the thymus before export to the peripheral circulation. As T cells differentiate and expand in the periphery, each T cell subset is differentially regulated and subjected to distinct homeostatic signals. For example, int

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Holderried, Tobias A. W., Hye-Jung Kim, Philipp A. Lang, and Harvey Cantor. "CD8+ Treg - From Mouse To Man." Blood 122, no. 21 (2013): 3474. http://dx.doi.org/10.1182/blood.v122.21.3474.3474.

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Abstract T cell-mediated regulation of the immune response to self and foreign antigens is essential to maintain immune homeostasis and prevent autoimmune tissue destruction. The majority of studies addressing this issue, both in mice and humans, have focused on the contribution of CD4+CD25+FOXP3+ regulatory T cells. The contribution of regulatory CD8+ T cells has not been appreciated until recently. Recent studies have identified a small subset of IL-15 dependent CD8+ regulatory T cells (Treg) that is essential for maintenance of self- tolerance and prevention of autoimmune disease in mice. E

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Sun, Juan, Yiming Yang, Xiaona Huo, et al. "Efficient Therapeutic Function and Mechanisms of Human Polyclonal CD8+CD103+Foxp3+ Regulatory T Cells on Collagen-Induced Arthritis in Mice." Journal of Immunology Research 2019 (February 19, 2019): 1–12. http://dx.doi.org/10.1155/2019/8575407.

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Objective. To investigate the potential therapeutic effect in a rheumatoid arthritis model of stable human CD8+ regulatory T cells (hCD8+Tregs) induced by TGF-β1 and rapamycin (RAPA) in vitro. Methods. Human CD8+T cells were isolated from human peripheral blood mononuclear cells and induced/expanded with TGF-β1 and RAPA along with anti-CD3/28 beads and IL-2 in vitro and harvested as hCD8+Tregs. The phenotypes, suppressive characteristics, and stability of the hCD8+Tregs in an inflammatory microenvironment were examined in vitro. Human CD8+Tregs were transfused into an acollagen-induced arthrit

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Ragab, Ahmed A. Y., Margaret Doyle, Jiachen Chen, Yuan Fang, Kathryn Lunetta, and Joanne Murabito. "AGING-RELATED IMMUNE CELLS PHENOTYPES AND ALL-CAUSE MORTALITY IN THE FRAMINGHAM HEART STUDY." Innovation in Aging 7, Supplement_1 (2023): 862. http://dx.doi.org/10.1093/geroni/igad104.2776.

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Abstract Almost 2 billion people will likely be above the age of 60 by 2050. Aging is a process that is intrinsically complicated. One of the measures for immune system senescence is aging related immune cells phenotypes (ARIP)s. Besides CD8/CD4 ratio, new immunosenescence phenotypes have been proposed. The associations between ARIPs and all-cause mortality during long-term follow up is understudied. We profiled immune cells using flow cytometry and prospectively investigated ten different ARIPs, namely, CD4+CD27-, CD4+CD28-CD27-, CD8+CD27-, CD8+CD28-CD27-, CD4+/CD8+ ratio, CD4+(Tnaive/(T Cent

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Fan, Huahua, Xiaona Huo, Juan Sun, Yiming Yang, and Xiao Li. "Efficient Induction and Expansion Of CD8+CD28+Foxp3+ Regulatory T Cells By TGF-beta1 and Rapamycin." Blood 122, no. 21 (2013): 190. http://dx.doi.org/10.1182/blood.v122.21.190.190.

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Abstract Background Although extensive studies have focused on the CD4+CD25+Foxp3+Tregs in recent years, CD8+Tregs have also been reported to play important roles in maintenance of immune tolerance. Adoptive transfer of CD8+Tregs in rodents can prevent or treat autoimmune diseases, allograft rejection or graft-versus-host disease. Objective Several approaches for induction of Ag-specific CD8+Tregs have been reported, but there is currently no reliable protocol for the ex vivo induction and large-scale expansion of human polyclonal CD8+CD28+Foxp3+Tregs. Our research was designed to investigate

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Liu, Chao, Yi Sun, Jinbo Yue, and Jinming Yu. "Prognostic interaction of smoking history with circulating regulatory T cells in advanced non-small cell lung cancer." Journal of Clinical Oncology 37, no. 15_suppl (2019): e14030-e14030. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14030.

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e14030 Background: Smokers with non-small cell lung cancer (NSCLC) respond better to the inhibition of programmed cell death-1 (PD-1) with pembrolizumab than non-smokers do, which may be accounted for by the fact that smoking induces higher neoantigens and increased immunogenicity. Our investigation sought to highlight the prognostic interaction of smoking history with circulating regulatory T cells (Treg), CD3+, CD4+, and CD8+ T cells in advanced NSCLC. Methods: Using ﬂow cytometry, we assessed levels of circulating Treg cells, CD8+ T cells, CD4+ T cells, and CD3+ T cells in 106 eligible pati

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Mansoori, Mohammad Nizam, Olena Kamenyeva, Juraj Kabat, and Ethan M. Shevach. "Regulatory T cells suppress antigen-specific CD8+ T cells in vivo by modulating the immune-synapse." Journal of Immunology 206, no. 1_Supplement (2021): 96.05. http://dx.doi.org/10.4049/jimmunol.206.supp.96.05.

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Abstract T Regulatory cells (Tregs) plays an important role in regulating self and foreign antigens related immune response by different mechanisms. Recent studies have shown that antigen-specific Treg suppress CD4+ effectors T cells in vitro and in vivo by depleting peptide-MHC-II complexes from the DC surface. These, results raise questions as to how Treg suppress CD8+ T effectors, particularly in vivo. To explore Treg mediated suppression of CD8+ T cells, we generated CD4+ iTregs from OT-II mice specific for Ova323–339 in association with I-Ab and determined their capacity to suppress CD8+

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Srinivasan, Saranya, Ma Chaoyu, Shruti Mishra, Liwen Wang, Kenneth Fan, and Nu Zhang. "Age-dependent changes in the regulatory program of CD8+ Regulatory T cells (CD8+ Tregs)." Journal of Immunology 208, no. 1_Supplement (2022): 167.03. http://dx.doi.org/10.4049/jimmunol.208.supp.167.03.

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Abstract Regulatory T cells (Tregs) help maintain the immune homeostasis. Any defect in the Tregs causes dysregulated immune responses that leads to risk of infection, autoimmunity, and cancer. Increased morbidity in the elderly patients is due to age-related changes in the immune system called immune aging. Despite several age-related studies in immune cells, immune aging in CD8+ Tregs are poorly characterized. With the growing number of evidence for the presence of various CD8+ Treg subset, our group has recently discovered that mice with knock out of specific CD8+ Treg subset characterized

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Preston, Claudia, Matthew Maurer, Ann Oberg, et al. "CD4+CD25+FOXP3+ regulatory T cells and association with survival in epithelial ovarian cancer (74.9)." Journal of Immunology 188, no. 1_Supplement (2012): 74.9. http://dx.doi.org/10.4049/jimmunol.188.supp.74.9.

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Abstract Ovarian cancer is an immune reactive tumor with a complex suppressive network that blunts immune eradication. One putative pathway of evasion may be recruitment of CD4 regulatory T cells (Treg) into the tumor microenvironment. This study investigated the association of tumor infiltrating Tregs in ovarian cancer patients with poor survival. Methods: Immunofluorescence of intraepithelial CD4+CD25+FOXP3+ Tregs, CD3+ and CD8+ cells was performed in tumors of 52 ovarian cancer patients. Average and maximum count of cells were associated with survival via Cox regression models and summarize

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Zhang, Hong, Anil Pahuja, Kelly Lundsten, et al. "Sustained Treg expansion by repeated in vivo injection of anti-TNFRSF25 mAb (P4142)." Journal of Immunology 190, no. 1_Supplement (2013): 191.17. http://dx.doi.org/10.4049/jimmunol.190.supp.191.17.

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Abstract FOXP3+ Tregs play key roles in maintenance of immune tolerance and autoimmune reactions. TNFRSF25 (also known as DR3) is one of the more recently discovered TNFRSF member, which is expressed by mouse Tregs, naïve CD4, CD8, NKT cells and TLR4-induced DC and macrophages. A significant Treg in vivo expansion by TNFRSF25 stimulation has been reported. Here, we show that by single dose i.p. injection of an agonistic mAb, 4C12, Treg expansion starts to be observed on day 3, reached a peak (up to 30-40% of total CD4+ T-cells) on day 5-6, and then returned to baseline (5-7%) by day 10. Upon

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Han, Jing Light, Jason Zimmerer, Qiang Zeng, Sachi Chaudhari, Christopher Breuer, and Ginny L. Bumgardner. "Deficiency of antibody-suppressor CXCR5+CD8+ T cells (not CD4+ Tregs) drives high alloantibody production in CCR5 KO kidney transplant recipients." Journal of Immunology 208, no. 1_Supplement (2022): 175.09. http://dx.doi.org/10.4049/jimmunol.208.supp.175.09.

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Abstract Kidney transplant (KTx) into CCR5 KO mice is an excellent model to study AMR immunobiology due to a heightened humoral response posited to be secondary to impaired CD4+Treg cell trafficking to the allograft. We have observed that adoptive cell therapy (ACT) with alloprimed CXCR5+CD8+ T cells mediates significant reduction of alloAb titer in CCR5 KO KTx recipients. We hypothesized that CXCR5+CD8+ T cells are more potent inhibitors of alloAb production than CD4+Tregs. We found that CCR5 KO recipients have significantly fewer CXCR5+CD8+ T cells (782±183 vs 2058±167 cells/mm3) and graft-i

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Schuler, Patrick, William Buchanan, Sharon Riddler, Theresa Whiteside, Macatangay Bernard, and Charles Rinaldo. "Reverse correlation between CD39+CD25+ Treg and activated CD8+ T cells / NK cells in HIV-1- patients with low CD4 cell counts (105.48)." Journal of Immunology 186, no. 1_Supplement (2011): 105.48. http://dx.doi.org/10.4049/jimmunol.186.supp.105.48.

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Abstract The role of regulatory T cells (Treg) in HIV has been studied intensely but remains unclear regarding their effect on cellular immune activation. Frequencies of CD4 and CD8 T cells, CD39+CD25+ Treg, Th17 cells, MDSC, B cells, NK cells and the activation status of T cells (CD38+HLADR+) were determined by flow cytometry in 10 healthy controls and 32 HIV-1+ patients. Immunosuppressive functions of single-cell sorted Treg were determined in the CFSE proliferation assay. Cytokine production (IL1b, 2, 4, 5, 6, 8, 10, INFg, TNFa, GM-CSF), C-reactive protein and soluble CD14 were measured in

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Holderried, Tobias A. W., Pia Sauerborn, Hye-Jung Kim, Harvey Cantor, Dominik Wolf, and Peter Brossart. "Human CD8+ Treg after Allogeneic Stem-Cell Transplantation." Blood 128, no. 22 (2016): 2243. http://dx.doi.org/10.1182/blood.v128.22.2243.2243.

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Abstract Murine CD8+ regulatory T cells (Treg) are characterized by expression of the cell surface triad CD44, CD122 and Ly49 and require the transcription factor Helios for stable regulatory function. This regulatory CD8+ T cell subset recognizes target cells through the recognition of the Qa-1-molecule (HLA-E in man), resulting in perforin-dependent elimination of target cells. Qa-1 is a MHC class Ib molecule that presents a limited repertoire of peptides that generally serve as an indicator of cellular activation and stress. Until now, CD4+ follicular T helper cells (TFH) and CD8+ effector

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Crane, Courtney, Justin Bowser, Rachael Fasnacht, et al. "A NEWLY DISCOVERED REGULATORY CD8 T CELL NETWORK HAS THE POTENTIAL TO REGULATE AND ELIMINATE PATHOGENIC CD4 T CELLS IN AUTOIMMUNE MEDIATED DISEASE OF THE GUT." Inflammatory Bowel Diseases 28, Supplement_1 (2022): S55. http://dx.doi.org/10.1093/ibd/izac015.086.

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Abstract INTRODUCTION Several groups have described a subset of CD8 T cells with immunosuppressive characteristics in inflammatory disease settings. The increased prevalence of a defined subset of CD8 T cells and correlation to disease has been reported in mouse and human autoimmune diseases, suggesting a protective role for select CD8 T cells in autoimmunity. We hypothesized that a dysregulated regulatory CD8 T cell (CD8 Treg) network was similarly involved in the pathology of autoimmune diseases of the gut, including Celiac disease, Crohn’s, and Ulcerative Colitis. Recently, investigators ha

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Deyev, Vadim, Melinda Roskos, Robert B. Levy, and Eckhard R. Podack. "TNFR25 Expression on CD4+CD25+ T Cells: Down Modulation of Regulatory Activity." Blood 108, no. 11 (2006): 3165. http://dx.doi.org/10.1182/blood.v108.11.3165.3165.

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Abstract TNFR25 (“DR3”) is a member of the TNF receptor family that is expressed by activated CD4+ and CD8+ T cells. To determine if activated CD4+CD25+ T cells also expressed this TNFR family molecule, B6 CD4+CD25+ T cells were stimulated with anti-CD3/CD28 coated beads (kind gift of Dr. B. Blazar, U. Minn.) and expanded for 3–4 days. TNFR25 expression was readily detected on CD4+CD25+ FoxP3+ T cells. Since other members of the TNF receptor family (GITR, OX40, 4–1BB) are known to influence T regulatory cell function, we investigated whether TNFR25 signaling can regulate CD4+CD25+ T cell activ

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Urbieta, Maite, Isabel Barao, Monica Jones, William J. Murphy, and Robert B. Levy. "Regulation of Hematopoietic Colony Forming Cells by CD4+CD25+ T Cells: A Role for T Regulatory Cells in Hematopoiesis?." Blood 108, no. 11 (2006): 3181. http://dx.doi.org/10.1182/blood.v108.11.3181.3181.

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Abstract CD4+CD25+ T cells (Treg) comprise a small population within the normal peripheral CD4 T cell compartment. Their primary physiological role appears to be the regulation of autoimmune responses, however, in recent years it has been established that they can modulate anti-tumor as well as transplantation responses. Treg cells have been found to exert their affects on multiple types of immunologically relevant cells including CD4, CD8 and NK populations. Although model dependent, cytokines including TGFβ and IL-10 have been identified as mediators of this population’s regulatory activity

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Gonzalez-Rey, Elena, Alejo Chorny, Amelia Fernandez-Martin, Doina Ganea, and Mario Delgado. "Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells." Blood 107, no. 9 (2006): 3632–38. http://dx.doi.org/10.1182/blood-2005-11-4497.

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Induction of antigen-specific tolerance is critical for autoimmunity prevention and immune tolerance maintenance. In addition to their classical role as sentinels of the immune response, dendritic cells (DCs) play important roles in maintaining peripheral tolerance through the induction/activation of regulatory T (Treg) cells. The possibility of generating tolerogenic DCs opens new therapeutic perspectives in autoimmune/inflammatory diseases. Characterizing endogenous factors that contribute to the development of tolerogenic DCs is highly relevant. We here report that the immunosuppressive neu

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Hall, Bruce Milne, Nirupama Darshan Verma, Catherine Margaret Robinson, et al. "Recently alloactivated CD4+CD8−CD25+T regulatory cells express CD8alpha and are potent suppressor cells." Journal of Immunology 202, no. 1_Supplement (2019): 57.20. http://dx.doi.org/10.4049/jimmunol.202.supp.57.20.

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Abstract Therapy with antigen-specific CD4+CD25+ T regulatory cells (Treg) for induction of transplant tolerance is desirable, as naïve thymic Treg (tTreg) are non-antigen specific and weak suppressor cells. Naïve tTreg from DA rats cultured with fully allogeneic PVG stimulator cells and IL-2 express IFN-gamma receptor (IFNGR) and IL-12 receptor beta2 (IL-12Rb2) and are more potent alloantigen-specific regulators that we call Ts1 cells. This study examined other markers that could identify the activated alloantigen-specific Treg as a subpopulation within the CD4+CD25+Foxp3+Treg. After culture

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Tran, Dat, Ossama Maher, Charlotte Rivas та Shannon Moree. "Reduced and skewed TCR Vβ repertoire in CD8 compared to Foxp3+ regulatory T cells in acute gastrointestinal graft versus host disease (TRAN1P.947)". Journal of Immunology 194, № 1_Supplement (2015): 140.29. http://dx.doi.org/10.4049/jimmunol.194.supp.140.29.

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Abstract It is unclear if skewing of TCR repertoire in CD4, CD8 and Foxp3+Tregs plays a role in acute gastrointestinal (GI) GVHD. This prospective clinical study examined the TCR Vβ diversity among CD4, CD8 and Foxp3+Tregs from 18 adult patients (median age 53) post allogeneic stem cell transplant (SCT) at day 80 with acute GI GVHD (giGVHD, &gt;grade 1, n=9) vs. nonGVHD (n=9). Fresh PBMC were analyzed by FACS using IOTest Beta Mark 24 TCR Vβ and Foxp3 (236A/E7)/Helios eBioscience kits. Mann Whitney test was used. Mean %CD4 was lower in giGVHD vs. nonGVHD (44vs72%, p=0.02) while no differen

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Liu, Hsin-Yu, Christophe Pedros, Ann Balancio, Kok-Fai Kong, and Amnon Altman. "Protein kinase C-eta is required for Treg-mediated suppression of anti-tumor and viral immunity." Journal of Immunology 204, no. 1_Supplement (2020): 244.14. http://dx.doi.org/10.4049/jimmunol.204.supp.244.14.

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Abstract We previously reported that protein kinase C-eta plays an important role in the contact-dependent suppressive activity of Tregs via its association with CTLA4, and that PKC-eta-deficient (Prkch−/−) Tregs fail to suppress anti-melanoma tumor immunity. Here we extend this study to a genetically engineered mouse model of HCC driven by CRISPR-Cas9-driven deletion of Pten and p53. In the Pten-p53 HCC model, Prkch Treg-specific conditional knockout (cKO) mice developed a lower tumor incidence, fewer tumors, lower degree of steatosis phenotype, and showed higher intratumoral CD4+ T cells tha

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Beres, Amy, Dipica Haribhai, Chelsea Tessler-Verville, et al. "Induction of a Novel Population of CD8+ Foxp3+ Regulatory T Cells During Graft Versus Host Disease." Blood 118, no. 21 (2011): 821. http://dx.doi.org/10.1182/blood.v118.21.821.821.

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Abstract Abstract 821 Regulatory T cells defined as CD4+ and expressing the transcription factor Foxp3 have been shown to play a pivotal role in mitigating the severity of graft versus host disease (GVHD). In the course of studies designed to define the functional role of various CD4+ Treg populations in GVHD biology, we identified a novel population of CD8+ T cells that expressed Foxp3 and were induced early during this disease. While this population has been reported in patients with autoimmune disorders, the role of CD8+ Foxp3+ T cells in GVHD is unknown. To delineate the significance of th

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Yang, Zhi-Zhang, Anne J. Novak, Mary J. Stenson, Thomas E. Witzig, and Stephen M. Ansell. "Intratumoral Treg Cells Completely Inhibit the Induction and Function of Tumor-Infiltrating CD8+ T-Cells in B-Cell NHL." Blood 106, no. 11 (2005): 3311. http://dx.doi.org/10.1182/blood.v106.11.3311.3311.

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Abstract Background: Numerous studies have shown that lymphoma B-cells are resistant to CTL-mediated death, however the underlying mechanism for this resistance is not clear. In previous work, we have identified a subset of CD4+CD25+ T-cells overrepresented in the tumor sites of B-cell NHL that display a phenotype compatible with regulatory T cells (Treg cells). These cells express high levels of Foxp3 and CTLA-4, and are capable of suppressing the proliferation and cytokine production of autologous infiltrating CD4+CD25- T cells in B-cell NHL. Goal: To explore whether Treg cells exert a suppr

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Gardell, Jennifer L., Daniel Boster, Justin Bowser, et al. "A KIR x CD8 targeting bispecific modulator enhances regulatory CD8 T cell functions, and reduces inflammation in models of autoimmune disease." Journal of Immunology 210, no. 1_Supplement (2023): 85.17. http://dx.doi.org/10.4049/jimmunol.210.supp.85.17.

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Abstract INTRODUCTION: We have characterized a subset of CD8 T cells (CD8 Treg) with immunosuppressive characteristics in inflammatory disease settings. CD8 Treg activation results in their oligoclonal expansion and elimination of pathogenic CD4 T cells. Here we describe a bispecific CD8 Treg modulator that activates autoimmune patient derived CD8 Treg resulting in the cytolytic elimination of pathogenic CD4 T cell in vitro, ex vivo, and in vivo. METHODS: We tested target and cell binding of a novel bispecific CD8 Treg modulator by Octet and flow cytometry. The functional impact was evaluated

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Mansoori, Mohammad Nizam, and Ethan Menahem Shevach. "Regulatory T cells suppression of antigen-specific CD8+ T cells in vivo is contact-dependent." Journal of Immunology 204, no. 1_Supplement (2020): 72.1. http://dx.doi.org/10.4049/jimmunol.204.supp.72.1.

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Abstract T Regulatory cells (Tregs) plays an important role in regulating immune mediated responses against self and foreign antigens by various known and unknown mechanisms. Recent studies have shown that antigen-specific iTreg suppress CD4+ effectors T cells in vitro and in vivo by depleting peptide-MHC-II complexes from the DC surface. These, results raise questions as to how Treg suppress CD8+ T effectors, particularly in vivo. To explore Treg mediated suppression of CD8+ T cells, we generated CD4+ iTregs from OT-II mice specific for Ova323–339 in association with I-Ab and determined their

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Wasnik, Samiksha, David J. Baylink, Jianmei Leavenworth, Chenfan Liu, Hongzheng Bi, and Xiaolei Tang. "Towards Clinical Translation of CD8+ Regulatory T Cells Restricted by Non-Classical Major Histocompatibility Complex Ib Molecules." International Journal of Molecular Sciences 20, no. 19 (2019): 4829. http://dx.doi.org/10.3390/ijms20194829.

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In central lymphoid tissues, mature lymphocytes are generated and pathogenic autoreactive lymphocytes are deleted. However, it is currently known that a significant number of potentially pathogenic autoreactive lymphocytes escape the deletion and populate peripheral lymphoid tissues. Therefore, peripheral mechanisms are present to prevent these potentially pathogenic autoreactive lymphocytes from harming one’s own tissues. One such mechanism is dictated by regulatory T (Treg) cells. So far, the most extensively studied Treg cells are CD4+Foxp3+ Treg cells. However, recent clinical trials for t

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Aliazis, Konstantinos, Anthos Christofides, Halil-Ibrahim Aksoylar, et al. "Specific PD-1 Deletion on Regulatory T Cells Leads to Enhanced Anti-Tumor Responses." Blood 142, Supplement 1 (2023): 2551. http://dx.doi.org/10.1182/blood-2023-174422.

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Programmed cell death 1 (PD-1) is a T cell inhibitory receptor and the most extensively exploited therapeutic target of checkpoint immunotherapy in cancer. Ligation of PD-1 by its ligands PD-L1 or PD-L2 leads to inhibition of CD4 + and CD8 + T cell responses. However, very little is known about the specific role of PD-1 in regulatory T (Treg) cells. Previous studies have shown that PD-1 engagement during induction of Treg polarization by TCR/CD28 signaling in the presence of IL-2 and TGF-β promoted the generation and expansion of Treg cells with potent suppressive function. It has also been sh

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Iwamoto, Miki, Ken-ichi Matsuoka, Yusuke Meguri, et al. "Very Early Dynamics of Regulatory T-Cell Chimerism Significantly Varies According to the Donor Sources: Implication for Basic Immune Pathogenesis of Engraftment Phase." Blood 128, no. 22 (2016): 4575. http://dx.doi.org/10.1182/blood.v128.22.4575.4575.

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Abstract Post-transplant expansion of donor-derived T cells has crucial impact on the early clinical events including graft engraftment and acute graft-versus-host disease. Flowcytometry-based method enables us to analyze the lymphocyte chemerism in the very early phase after HSCT and recent reports have shown that T-cell achieved donor-chimerism in the first two weeks in the majority cases. However, the very early dynamics of each T-cell subset, including CD4+Foxp3+ regulatory T cells (Tregs), has not been well characterized. Since the early expansion of Tregs and other CD4+ and CD8+ conventi

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Kim, Yong-Hee, Abir K. Panda, and Ethan M. Shevach. "Treg cell depletion in adult mice results in activation of antigen-presenting cells prior to fatal autoimmune disease." Journal of Immunology 210, no. 1_Supplement (2023): 248.03. http://dx.doi.org/10.4049/jimmunol.210.supp.248.03.

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Abstract Studies in mice expressing the diphtheria toxin receptor (DTR) exclusively on regulatory T (Treg) cells (Foxp3-DTR mice) demonstrated the critical importance of Treg cells in maintaining normal immune homeostasis. Adult Foxp3-DTR mice injected with DT begin to die from day 10 after DT treatment. Marked expansion of almost all immune cell types was observed prior to death. The purpose of the present studies was to examine in-depth changes in lymphocytes and antigen-presenting cells at early time points after Treg depletion to determine the most critical cell types controlled by Treg in

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Manuszak, Claire, Martha Brainard, Emily Thrash, F. Stephen Hodi, and Mariano Severgnini. "Standardized 11-color flow cytometry panel for the functional phenotyping of human T regulatory cells." Journal of Biological Methods 7, no. 2 (2020): e131. http://dx.doi.org/10.14440/jbm.2020.325.

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T regulatory cells (Tregs) are a cell subset that can suppress immune responses to maintain homeostasis and self-tolerance. In some scenarios, the immunosuppressive nature could be associated to other pathological developments such as autoimmune diseases and cancers. Due to the importance of Tregs in disease pathogenesis, we developed and validated an 11-color flow cytometry panel for phenotypic and functional detection of Treg markers using healthy human donor peripheral blood mononuclear cells (PBMCs). Our panel contains 4 Treg surface proteins and 2 functional cytokines as well as T-lymphoc

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Lui, Jenbon, Priya Devarajan, Sarah Teplicki, Jason Miska, and Zhibin Chen. "Gut-associated cross-differentiation of T lymphocyte lineages (LYM7P.726)." Journal of Immunology 192, no. 1_Supplement (2014): 193.14. http://dx.doi.org/10.4049/jimmunol.192.supp.193.14.

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Abstract Peripheral regulatory T cells engage in a necessary role in maintaining the volatile balance between the normal flora of the gut and the host immune system. However, the clonal origin of peripheral Treg cells is not well understood and has proven difficult to elucidate in the presence of naturally occurring thymic Treg cells. We hypothesized that the gut-associated environment enables cross differentiation of the CD8 T cell lineage to CD4 Treg cells for the regulation of immune cell homeostasis. Our preliminary examination found evidence for cross-differentiation from the CD8 lineage

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Drerup, Justin Michael, Alvaro Souto Padron, Wanjiao Chen, Curtis Anthony Clark, and Tyler Jay Curiel. "Manipulation of IL-2 signals by IL-2/antibody complex and CD25 blockade improves tumor immunity, reprograms regulatory T cells, and augments CD8+ central memory in an ovarian cancer model." Journal of Immunology 196, no. 1_Supplement (2016): 212.22. http://dx.doi.org/10.4049/jimmunol.196.supp.212.22.

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Abstract We used a defined IL-2/αIL-2 complex that directs IL-2 to stimulate only intermediate-affinity IL-2 receptor (CD122/132) to promote tumor rejection and avoid regulatory T cell (Treg) expansion. However, it is unknown if IL-2/αIL-2 alters Treg function, as Tregs also express CD122/132. After challenge with ID8agg ovarian cancer (OC) cells, IL-2/αIL-2 greatly reduced tumor burden, and increased IFN-γ, TNF-α, CD44, and CD25 in CD4+ non-Tregs and CD8+ T cells, as expected. IL-2/αIL-2 was clinically effective, yet it lowered the ascites CD8+/FoxP3+ Treg ratio and increased per cell FoxP3 l

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Foureau, David, Iain McKillop, Chase Jones, Asim Amin, Richard White, and Jonathan Salo. "Skin Tumor Responsiveness to IL-2 Treatment Correlates to CD8 Treg Expansion in an Immunocompetent Mouse Model. (100.15)." Journal of Immunology 184, no. 1_Supplement (2010): 100.15. http://dx.doi.org/10.4049/jimmunol.184.supp.100.15.

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Abstract CD8 Tregs play an important role in graft tolerance and autoimmune disease status. Interleukin-2 (IL-2) induces Foxp3 expression by activated human CD8 T cells in vitro, and expands circulating CD8 Foxp3+ T cells in melanoma patients. IL-2 is FDA approved for the treatment of advanced melanoma, yet positive outcomes are limited. The aim of this study was to determine the phenotype and distribution of CD8 Foxp3 expressing T cells in skin tumor-bearing mice receiving IL-2. In normal or skin tumor-bearing mice, Foxp3 expressing CD8 T cells were a rare but naturally occurring cell subset.

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Fullerton, Benjamin, Robyn Gartrell, Thomas Enzler, et al. "872 Neoadjuvant chemoradiotherapy enhances T cell infiltration in pancreatic ductal adenocarcinoma but high percentage of regulatory T cells associates with poor survival." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (2020): A924—A925. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0872.

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BackgroundCurrently, diagnosis with pancreatic ductal adenocarcinoma (PDAC) renders an almost intrinsically poor patient prognosis. Despite complete surgical resection and intense neoadjuvant and/or adjuvant treatment the great majority of patients will ultimately relapse and die from the disease. Further, PDAC has been characterized as highly immune resistant. It is speculated that radiation, chemotherapy, or chemoradiation cause the release of tumor antigens and inflammatory cytokines eventually leading to increased immunogenicity of PDAC.MethodsWe used computational quantitative multiplex i

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Kim, Jung-Sik, Kyeo-Rae Han, and Chung-Gyu Park. "Novel Consistently Ex-vivo Expanded CD8+CD25+FoxP3+Treg Cells Prolongs the Allogeneic Islet Survival." Journal of Immunology 200, no. 1_Supplement (2018): 55.39. http://dx.doi.org/10.4049/jimmunol.200.supp.55.39.

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Abstract In addition to CD4+ regulatory T cells(Tregs), adoptive transfer of CD8+CD25+FoxP3+T cells is emerging as an alternative adjunctive therapy to diminish current reliance on lifelong, nonspecific immunosuppression after transplantation. Here we evaluated the possible therapeutic application of consistently ex-vivo expanded mouse CD8+CD25+FoxP3+T cells to prevent the rejection of allogeneic islets. Around 80% of mouse CD8+CD25+T and CD4+CD25+T cells expressed FoxP3+T cells in spleen. Higher level of FoxP3 was expressed in CD8+Tregs compared to CD4+Tregs. Ex-vivo enriched CD8+CD25+Treg ce

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Zhu, Qin, Jiaqi Yuan, Yuqiong He, and Yu Hu. "The Effect of miR-520b on Macrophage Polarization and T Cell Immunity by Targeting PTEN in Breast Cancer." Journal of Oncology 2021 (October 6, 2021): 1–19. http://dx.doi.org/10.1155/2021/5170496.

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Background. Breast cancer is the most common cancer in women. miR-520b had binding sites with PTEN through the bioinformatics prediction. But few studies have been conducted on miR-520b and PTEN in breast cancer. We aimed to explore the effect of miR-520b and PTEN on breast cancer and the mechanisms involved. Methods. Clinical samples of breast cancer were collected. Bioinformatics analysis was performed to screen the differentially expressed miRNAs. CD4 T cells and CD8 T cells were cocultured with MCF-7 cells in the Transwell system. Moreover, MCF-7 cells and M0 macrophage cocultured cell lin

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