Similar Datasets
Project description:Chromatin accessibility changes of Fli1ko vs WT in CD8 T cells
| PRJNA630255 | ENA
Project description:CD8+ T lymphocytes differentiate from effector to memory cells following antigen clearance, with prolonged IL-2 production characterizing functional cytotoxic T lymphocytes (CTLs). To identify transcription factors associated with sustained IL-2 production, we compared influenza virus-specific and cytomegalovirus-specific CTLs, identifying Basic Leucine Zipper ATF-Like Transcription Factor 3 (BATF3) as a key candidate gene. BATF3 overexpression significantly enhanced cell proliferation in both virus-specific CTLs and CD19 chimeric antigen receptor T (CAR-T) cells while reducing cytokine production. ATAC-seq analysis revealed that BATF3 overexpression dynamically regulates chromatin accessibility, affecting diverse cellular processes including cytoskeletal organization, metabolic pathways, and cellular survival signaling. BATF3 specifically facilitated the critical transition from effector to memory phase. These findings establish BATF3 as a master regulator of CD8+ T cell fate determination through dynamic chromatin remodeling mechanisms.
2026-04-10 | GSE325835 | GEO
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: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: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:Fli1 as transcriptional safeguard that restrains effector CD8 T cell differentiation
| PRJNA630251 | ENA