Sequence analysis of CD4 Treg, CD8 Treg and CD8 effector
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE150628 | GEO | 2020/05/16
REPOSITORIES: GEO
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Project description:The maintenance of immune homeostasis requires regulatory T cells (Tregs). Given their intrinsic self-reactivity, Tregs must stably maintain a suppressive phenotype to avoid autoimmunity. We report that impaired expression of the transcription factor (TF) Helios by FoxP3+ CD4 and Qa-1-restricted CD8 Tregs results in defective regulatory activity and autoimmunity in mice. Helios-deficient Treg develop an unstable phenotype during inflammatory responses characterized by reduced FoxP3 expression and increased effector cytokine expression secondary to diminished activation of the STAT5 pathway. CD8 Treg also require Helios-dependent STAT5 activation for survival and to prevent terminal T cell differentiation. Definition of Helios as a key transcription factor that stabilizes regulatory T-cells in the face of inflammatory responses provides a genetic explanation for a core property of regulatory T-cells. We used microarrays to detail the global programs of gene expression by CD8 Treg (CD44+CD122+Ly49+) and conventional memory type of CD8 cells (CD44+CD122+Ly49-).
2015-09-15 | E-GEOD-73015 | biostudies-arrayexpress
Project description:Sequence analysis of CD4 Treg, CD8 Treg and CD8 effector
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Project description:Gene expression profile was compared between CD8+CD122+ T cells and CD8+CD122- T cells. mRNA taken from CD8+CD122+ cells or CD8+CD122- cells collected by cell sorting from C57BL/6 mice spleen was amplified and analyzed by using gene chip of Agilent.
2008-12-30 | E-GEOD-13890 | biostudies-arrayexpress
Project description:We report the transcriptome analysis of epidermal CD8 tissue resident memory T (TRM) cells from healthy human skin. Specifically, epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells from healthy human skin were sorted by FACS. Differential gene expression analysis revealed functional dichotomy of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells.
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Project description:Gene expression profile was compared between CD8+CD122+ T cells and CD8+CD122- T cells.
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Project description:Rationale: COPD is characterized by an abnormal regulatory T cell (Treg) response and increases in Th1 and Th17 cell responses. It is unclear if dysregulation of miRNAs within Treg alters the adaptive immunophenotype in COPD. Objectives: To compare the miRNA profile of COPD Treg cells with that of healthy controls and to explore the function of differentially expressed miRNAs. Methods: Treg cells (CD4+CD25+CD49-CD127-) and T effector (CD4+CD25-) cells were obtained from the peripheral blood of 4 nonsmokers, 4 healthy current smokers, and 4 COPD current smokers for analysis of miRNA expression, matching them for age and sex. We assessed expression initially by microarray analysis on the Illumina miRNA platform then conducted real time RT-PCR validation of the microarray results. 24 samples were analyzed. 8 from each patient group of healthy Normal, Healthy Smoker, and COPD Smoker.
2014-04-19 | E-GEOD-56923 | biostudies-arrayexpress
Project description:Rationale: COPD is characterized by an abnormal regulatory T cell (Treg) response and increases in Th1 and Th17 cell responses. It is unclear if dysregulation of miRNAs within Treg alters the adaptive immunophenotype in COPD. Objectives: To compare the miRNA profile of COPD Treg cells with that of healthy controls and to explore the function of differentially expressed miRNAs. Methods: Treg cells (CD4+CD25+CD49-CD127-) and T effector (CD4+CD25-) cells were obtained from the peripheral blood of 4 nonsmokers, 4 healthy current smokers, and 4 COPD current smokers for analysis of miRNA expression, matching them for age and sex. We assessed expression initially by microarray analysis on the Illumina miRNA platform then conducted real time RT-PCR validation of the microarray results.
2014-04-19 | GSE56923 | GEO
Project description:Regulatory T cells (Tregs) are a key mediator of resistance to cancer immunotherapy, including anti-PD-(L)1 immune checkpoint blockade (ICB). Tregs perpetually infiltrate tumors and hamper effective anti-tumor immunity. The mechanisms driving Treg infiltration into the tumor microenvironment (TME) and the consequence on CD8+ T cell exhaustion remains elusive. Herein, we report that heat shock protein gp96 (GRP94) is indispensable for Treg infiltration into the tumor, primarily through gp96’s roles in chaperoning integrins. Among various gp96-dependent integrins, we found that only LFA-1 (αL integrin) but not integrin αV, CD103 (αE) or β7 was required for Treg homing into the tumors. Loss of Treg infiltration into the TME by genetically deleting gp96/LFA-1 potently induces rejection of multiple ICB-resistant murine cancer models in a CD8+ T cell dependent manner without loss of self-tolerance. Moreover, gp96 deletion impeded Treg activation primarily by suppressing IL-2/phosphorylated STAT5 (pSTAT5) signaling pathway, which also contributes to tumor regression. Notably, by a mechanism in part through competing for IL-2 in the TME, intra-tumoral Tregs prevent activation of CD8+ tumor-infiltrating lymphocytes (TILs), drive TOX induction and induce bona fide CD8+ T cell exhaustion. By contrast, Treg ablation leads to a striking CD8+ T cell activation without TOX induction, demonstrating clear uncoupling of the two processes. Our study reveals that the gp96/LFA-1 axis plays a fundamental role in Treg biology and intratumoral CD8+ T cell exhaustion. We suggest that, Treg-specific targeting of gp96/LFA-1 represents a novel strategy for cancer immunotherapy without inflicting autoinflammatory conditions.
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Project description:Previous reports show that Ly49+CD8+ T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8+ T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalents of the Ly49 family, in the blood and inflamed tissues of various human autoimmune diseases. Moreover, KIR+CD8+ T cells can efficiently eliminate pathogenic gliadin-specific CD4+ T cells from Celiac disease (CeD) patients’ leukocytes in vitro. Furthermore, we observe elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 and influenza-infected patients, and correlate with disease severity and vasculitis in COVID-19. Expanded KIR+CD8+ T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8+ T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells.
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Project description:Thymic-derived natural T regulatory cells (nTregs) are characterized by functional and phenotypic heterogeneity. Recently, a small fraction of peripheral Tregs have been shown to express Klrg1, but it remains unclear the extent Klrg1 defines a unique Treg subset. Here we show that Klrg1+ Tregs represent a terminally differentiated Treg subset derived from Klrg1- Tregs. This subset is a recent antigen-responsive and a highly activated short-lived Treg population that expresses enhanced levels of Treg suppressive molecules and that preferentially resides within mucosal tissues. The development of Klrg1+ Tregs also requires extensive IL-2R signaling. This activity represents a distinct function for IL-2, independent from its contribution to Treg homeostasis and competitive fitness. These and other properties are analogous to terminally differentiated short-lived CD8+ T effector cells. Our findings suggest that an important pathway driving antigen-activated conventional T lymphocytes also operates for Tregs. Gene expression analysis was performed of this and other Treg subsets based on expression of CD62L, CD69, and Klrg1 to define the molecular properties of Klrg1+ Tregs and its relationship to other Treg subsets found in the peripheral immune tissues. Mice were euthanized, spleen cell preparations were made, and each Treg subset was isolated by FACS cell sorting. RNA was immediately prepared for processing.
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