Similar Datasets
Project description:Chromatin accessibility changes of Fli1ko vs WT in CD8 T cells
| PRJNA630255 | ENA
Project description:In response to acute infection, naive CD8+ T cells expand, differentiate into effector cells and then contract to a long-lived pool of memory cells after pathogen clearance. During chronic infections or in tumors, CD8+ T cells acquire an “exhausted” phenotype. Here we present genome-wide comparisons of chromatin accessibility and gene expression from endogenous CD8+ T cells responding to acute and chronic viral infection using ATAC-seq and RNA-seq. Acquisition of effector, memory or exhausted phenotypes was associated with stable changes in chromatin accessibility away from the naive T cell state. Regions differentially accessible between functional subsets in vivo were enriched for binding sites of transcription factors known to regulate these subsets, including E2A, BATF, IRF4, T-bet and TCF1. Exhaustion-specific accessible regions were enriched for consensus binding sites for NFAT and Nr4a family members, indicating that chronic stimulation confers a unique accessibility profile on exhausted cells.
2016-12-13 | GSE88987 | GEO
Project description:The transcriptional and epigenetic regulation of CD8+ T cell differentiation is critical for balancing pathogen eradication and long-term immunity by effector and memory CTLs. Here, we demonstrate that the Lysine Demethylase 6b (Kdm6b) is essential for the proper generation and function of effector CD8+ T cells during acute infection and tumor eradication. We found that cells lacking Kdm6b (either T cell-specific KO or knockdown utilizing shRNA strategies) show an enhanced generation of memory precursor and early effector cells upon acute viral infection in a cell-intrinsic manner. We also demonstrate that Kdm6b is indispensable for proper effector functions and tumor protection, and that memory CD8+ T cells lacking Kdm6b displayed a defective recall response. Mechanistically, we identified that Kdm6b, through induction of chromatin accessibility in key effector-associated gene loci, allows for the proper generation of effector CTLs. Our results pinpoint the essential function of Kdm6b in allowing chromatin accessibility in effector-associated genes, and identify Kdm6b as a potential target for therapeutics in diseases with dysregulated effector responses.
2021-02-25 | GSE161842 | GEO
Project description:CD4 T cells are essential for immunity to tuberculosis because they produce cytokines including interferon-γ. Whether CD4 T cells act as “helper” cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis (Mtb) is unknown. We compared transcriptomes of purified lung CD8 T cells from Mtb infected WT and MHCII KO mice. Using two independent models, we validated RNA-seq results and showed that CD4 T cell help enhanced CD8 effector functions and prevented CD8 T cell exhaustion. We demonstrated synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restricted intracellular bacterial growth in vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses against M. tuberculosis infection in vitro and in vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells.
2021-02-25 | GSE167439 | GEO
Project description:Repeat experiments of CD8+ pmel effector cells following one and two rounds of restimulation
2010-06-10 | E-GEOD-2348 | biostudies-arrayexpress
Project description:Comparative gene expression profiling of RNA-seq data for tumor-retained, tumor-egressed, and circulating effector CD44+ CD8+ T cells.
2023-01-20 | GSE203557 | GEO
Project description:CD8+ T cell differentiation traditionally results in the emergence of two subsets, Tc1 cells that produce interferon (IFN)-gamma and memory cells that mediate immune protection against pathogen infections. More recently, it has emerged that other specialized CD8+ T cell populations develop in immune responses and are critical to orchestrate complete immune protection. These subsets include tissue-resident memory (Trm) T cells, follicular cytotoxic T cells and two CD8+ T cell subsets that produce interleukin (IL)-17, namely, mucosal-associated invariant T (MAIT) cells and Tc17 cells. Here we investigated the role of TCF-1 in CD8+ T cell differentiation by using Assay for Transposase-Accessible Chromatin sequencing (ATAC-Seq) to determine the chromatin accessibility landscape of CD8+ T cells and how this is controlled by TCF-1. Loss of TCF-1 was associated with global changes in the chromatin architecture in CD8+ T cells leading to increased accessibility of Rorc and Tc17 effector genes IL-17a and IL-17f in Tc17 cells. In contrast, we observed reduced accessibility of Tbx21, Eomes and Irf4 loci in Tc17 cells, genes normally required for the induction of Tc1 and memory CD8+ T cells
2019-05-14 | GSE119839 | GEO
Project description:The goal of this study was to examine differences in gene expression of tumor specific CD8 T cells in an in vivo tumor mouse model after inhibition of galectin-3 protein expression by genetic knockout. Galectin-3 is thought to modulate CD8 T cell response by cross-linking cell surface glycoproteins Galectin-3 is a 31 kD carbohydrate-binding lectin that is over-expressed by many human malignancies. It also modulates T cell responses through a diverse array of mechanisms including induction of apoptosis, TCR cross linking in CD8+ T cells, and T cell receptor (TCR) down regulation in CD4+ T cells. We found that patients responding to a granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic pancreatic tumor vaccine developed post immunization antibody responses to galectin-3 on a proteomic screen. We used the HER-2/neu (neu-N) transgenic mouse model to study galectin-3 binding on adoptively transferred high avidity neu-specific CD8+ T cells derived from TCR transgenic mice. Here, we show that galectin-3 binds preferentially to activated antigen-committed CD8+ T cells only in the tumor microenvironment (TME). Galectin-3 deficient mice exhibit improved CD8+ T cell effector function and increased expression of several inflammatory genes when compared with wild type (WT) mice. We also show that galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3 mediated suppression of CD8+ T cells in vitro. Lastly, galectin-3 deficient mice have significantly elevated levels of circulating plasmacytoid dendritic cells (pDCs), which are superior to conventional dendritic cells (cDCs) in activating CD8+ T cells. Binding of galectin-3 to cell-surface glycoproteins on immune cells suppresses a pro-inflammatory immune response. Thus, inhibiting galectin-3 in conjunction with CD8+ T cell directed immunotherapies should enhance the tumor specific immune response. 3 different experimental groups were studied. Galectin-3 WT CD8 T cells adoptively transferred into Galectin-3 WT mice, galectin-3 WT CD8 T cells transferred into galectin-3 KO mice, and finally galectin-3 KO CD8 T cells transferred into galectin-3 KO mice. Galectin-3 WT CD8 T cells transferred into Galectin-3 WT mice were used as the reference group. Four biological replicates were submitted for each group, and adoptively transfered CD8 T cells were isolated 5 days post-adoptive transfer into tumor-bearing mice treated with a whole cell GM-CSF secreting vaccine. Cells were purified by cell sorting on the Thy1.2 surface marker.
2015-02-19 | E-GEOD-59454 | biostudies-arrayexpress
Project description:Coordination of cellular metabolism is essential for optimal T cell responses. Here, we identify cytosolic acetyl-CoA production as an essential metabolic node for CD8 T cell function in vivo. We show that acetyl-CoA derived from mitochondrial citrate via the enzyme ATP citrate lyase (Acly) is required for CD8 T cell responses to infection. However, ablation of Acly triggers an alternative, acetate-dependent pathway for acetyl-CoA production in T cells mediated by acyl-CoA synthetase short chain family member 2 (Acss2). Mechanistically, acetate fuels both the TCA cycle and cytosolic acetyl-CoA production, impacting T cell effector responses, acetate-dependent histone acetylation, and effector gene expression by altering chromatin accessibility. When Acly is functional, Acss2 is not required, suggesting acetate is not an obligate metabolic substrate for CD8 T cell function. However, deletion of Acly renders CD8 T cells dependent on acetate (via Acss2) to maintain acetyl-CoA production and effector function. Thus, together Acly and Acss2 coordinate cytosolic acetyl-CoA production in CD8 T cells to maintain chromatin accessibility and T cell effector function.
2024-08-01 | GSE262865 | GEO
Project description:Coordination of cellular metabolism is essential for optimal T cell responses. Here, we identify cytosolic acetyl-CoA production as an essential metabolic node for CD8 T cell function in vivo. We show that CD8 T cell responses to infection depend on acetyl-CoA derived from citrate via the enzyme Acly (ATP citrate lyase). However, ablation of Acly triggers an alternative, acetate-dependent pathway for acetyl-CoA production mediated by Acss2 (acyl-CoA synthetase short chain family member 2). Mechanistically, acetate fuels both the TCA cycle and cytosolic acetyl-CoA production, impacting T cell effector responses, acetate-dependent histone acetylation, and chromatin accessibility at effector gene loci. When Acly is functional, Acss2 is not required, suggesting acetate is not an obligate metabolic substrate for CD8 T cell function. However, deletion of Acly renders CD8 T cells dependent on acetate (via Acss2) to maintain acetyl-CoA production and effector function. Thus, together Acly and Acss2 coordinate cytosolic acetyl-CoA production in CD8 T cells to maintain chromatin accessibility and T cell effector function.
2024-07-04 | GSE267377 | GEO