Chromatin state in RA or LE540-treated human CD4+ T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE137714 | GEO | 2021/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:Asymmetric cell division (ACD) and the strength of initial T cell receptor (TCR) signaling are both implied to contribute to the establishment of cellular heterogeneity and CD8 T cell effector and memory differentiation. However, on a single cell level it remained unclear whether ACD generates progeny of different fates and whether the strength of TCR signaling affects this mechanism. Therefore, we developed experimental systems allowing monitoring the fate of single daughter cell progenies derived from an ACD either induced by weak or strong TCR stimulation by in vitro live imaging. We used the combinatorial expression of TCF1 and CD62L as markers indicating fate specification a few days after activation and analyzed the transcriptional profiles of in vitro generated CD62L+TCF1+ and CD62L-TCF1- cells derived from either antibody-induced (AB) activation or from gp33 (high affinity) or C6 (low affinity) peptide stimulation and compared them to in vivo generated effector and memory cells, respectively. Therefore, we sorted CD62L+TCF1+ and CD62L-TCF1- cells on day 6 post activation, followed by bulk RNA sequencing and found that CD62L+TCF1+ cells transcriptionally resembled in vivo generated memory cells, whereas CD62L-TCF1- cells were similar to in vivo generated effector cells.
2023-02-17 | E-MTAB-12563 | biostudies-arrayexpress
Project description:Vα24-invariant natural killer T cells (NKTs) possess innate antitumor properties that can be exploited for cancer immunotherapy. We have shown that the CD62L+ central memory-like subset drives NKT in vivo anti-tumor activity, but molecular mediators of NKT central memory differentiation remain unknown. Here, we demonstrate that CD62L+ NKTs express Wnt/β-catenin transcription factor LEF1 and maintain active Wnt/β-catenin signaling. CRISPR/Cas9-mediated LEF1 knockout reduced CD62L+ frequency after antigenic stimulation, while Wnt/β-catenin activator Wnt3a ligand increased CD62L+ frequency. LEF1 overexpression promoted NKT expansion and limited exhaustion following serial tumor challenge and was sufficient to induce a central memory-like transcriptional program in NKTs. In mice, NKTs expressing a GD2-specific chimeric antigen receptor (CAR) with LEF1 demonstrated superior control of neuroblastoma xenograft tumors compared to CAR-NKTs. These results identify LEF1 as a transcriptional activator of the NKT central memory program and advance development of NKT cell-based immunotherapy.
2022-11-07 | GSE217281 | GEO
Project description:Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naïve (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that TCM have a gene expression and cytokine signaling signature that lies between that of TN and TEM or TEMRA cells, whereas TEM and TEMRA are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that TEM and TEMRA cells strongly express genes with known importance in CD8 T cell effector function. In contrast, TCM are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish TCM and TEM/TEMRA at the molecular level and are consistent with the concept that TCM represent memory stem cells.
2005-01-01 | E-TABM-40 | biostudies-arrayexpress
Project description:We compared gene expression among central memory (CD62L+CD127+; pop1), effector memory (CD62L-CD127+; pop2), and terminal effector (CD62L-CD127-; pop4) isolated from a single-cell-derived WT1-specific CD4+ T cell clone.
2021-12-31 | GSE137142 | GEO
Project description:Memory T cells are important for protective immunity against infectious microorganisms. Such protection is achieved by cooperative action of memory T cell populations that differ in their tissue localization and functionality. We report on the identification of the fractalkine receptor CX3CR1 as marker for stratification of memory T cells with cytotoxic effector function from those with proliferative function in both, mice and man. Based on CX3CR1 and CD62L expression levels four distinct memory T cell populations can be distinguished based on their functional properties. Transcriptome and proteome profiling revealed that CX3CR1 expression was superior to CD62L to resolve memory T cell functionality and allowed determination of a core signature of memory T cells with cytotoxic effector function. This identifies a CD62Lhi CX3CR1+ memory T cell population with an identical gene signature to CD62LlowCX3CR1+ effector memory T cells. In lymph nodes, this so far unrecognized CD62LhiCX3CR1+ T cell population shows a distinct migration pattern and anatomic positioning compared to CD62LhiCX3CR1neg TCM. Furthermore, CX3CR1+ memory T cells were scarce or absent during chronic HBV, HCV and HIV infection in man and chronic LCMV infection in mice confirming the value of CX3CR1+ in understanding principles of protective immune memory. CD8+ T cells were isolated and directly assessed or incubated with DC or LSEC. After harvesting, cells were immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.
2016-06-10 | E-GEOD-63118 | biostudies-arrayexpress
Project description:Memory T cells are important for protective immunity against infectious microorganisms. Such protection is achieved by cooperative action of memory T cell populations that differ in their tissue localization and functionality. We report on the identification of the fractalkine receptor CX3CR1 as marker for stratification of memory T cells with cytotoxic effector function from those with proliferative function in both, mice and man. Based on CX3CR1 and CD62L expression levels four distinct memory T cell populations can be distinguished based on their functional properties. Transcriptome and proteome profiling revealed that CX3CR1 expression was superior to CD62L to resolve memory T cell functionality and allowed determination of a core signature of memory T cells with cytotoxic effector function. This identifies a CD62Lhi CX3CR1+ memory T cell population with an identical gene signature to CD62LlowCX3CR1+ effector memory T cells. In lymph nodes, this so far unrecognized CD62LhiCX3CR1+ T cell population shows a distinct migration pattern and anatomic positioning compared to CD62LhiCX3CR1neg TCM. Furthermore, CX3CR1+ memory T cells were scarce or absent during chronic HBV, HCV and HIV infection in man and chronic LCMV infection in mice confirming the value of CX3CR1+ in understanding principles of protective immune memory. CD8+ T cells were isolated and directly assessed. After harvesting, cells were immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.
2016-06-10 | E-GEOD-63144 | biostudies-arrayexpress
Project description:The memory B cell response consists of phenotypically distinct subsets that differ in their ability to respond upon antigen re-encounter. However, the pathways regulating the development and function of memory B cell subsets are poorly understood. Here we show that CD62L and CD44 are progressively expressed on mouse memory B cells and identify transcriptionally and functionally distinct memory B cell subsets. Bcl6 is important in regulating memory B cell subset differentiation with overexpression of Bcl6 resulting in impaired CD62L+ memory B cell development. Bcl6 regulates memory B cell subset development through control of a network of genes, including Bcl2 and Zeb2. Overexpression of Zeb2 impairs the development of CD62L+ memory B cells. Importantly, CD62L is also differentially expressed on human memory B cells following SARS-CoV-2 vaccination and identifies phenotypically distinct populations. Together, these data indicate that CD62L expression marks functionally distinct memory B cell subsets.
2023-12-07 | GSE247445 | GEO
Project description:Histone methylations play a major role in regulating the chromatin state and gene expression, yet little is known about their involvement in differential gene expression and function of memory CD8 T cells. Here, we report a genome-wide analysis of two histone H3 methylations (H3K4me3 and H3K27me3) and gene expression in naïve, central (TCM) and effector (TEM) memory CD8 T cells. Analysis of 16,314 annotated genes in CD8 T cell subsets revealed that gene expression were positively correlated with the levels of H3K4me3 and negatively correlated with the levels of H3K27me3 in these gene loci. The correlation between differential H3K4me3 orH3K27me3 levels with gene expressions in memory CD8 T cells displayed four distinct modes: repressive, active, poised, and bivalent, reflecting their complex regulation and different function of these genes. Furthermore, accessible chromatin states of different gene loci were preferentially influenced by different histone modifications as demonstrated here high levels of H3K9ac found in active gene loci without high levels of H3K4me3. These findings reveal a histone methylation based complex regulation of differential gene expression in memory CD8 T cells. Thus, change of chromatin structure mediated by histone methylation may serve a fundamental basis for the rapid transcriptional response of memory CD8 T cells. Keywords: Histone methylations, chromatin state, CD8 memory T cells Enriched naïve and memory CD8 T cells were purified into CD8+CD45RA+CD62L+ naïve T cells, CD8+CD45RA-CD62L+ central memory T cells (TCM), and CD8+CD45RA-CD62L- effector memory T cells (TEM) by a cell sorter (MoFlo; Dako Cytomation, Carpentaria, CA). Triplicates of each cell type were either used right away or incubated with anti-CD3 and anti-CD28 Ab (anti-CD3/CD28) coupled magnetic beads (Invitrogen) at the cell:bead ratio of 1:1 for 16 hours in RPMI-1640 with 10% Fetal bovine serum and penicillin (10 U/ml)/streptomycin (10 ug/ml) (Invitrogen). The freshly isolated and 16 hr stimulated cells from several donors as a pool were used for gene expression microarray analysis. All sample data was normalized to a standard control RNA labeled and hybed along with each sample and all data from the 3 replicates was averaged.
2009-03-06 | E-GEOD-14422 | biostudies-arrayexpress
Project description:Memory T cells are important for protective immunity against infectious microorganisms. Such protection is achieved by cooperative action of memory T cell populations that differ in their tissue localization and functionality. We report on the identification of the fractalkine receptor CX3CR1 as marker for stratification of memory T cells with cytotoxic effector function from those with proliferative function in both, mice and man. Based on CX3CR1 and CD62L expression levels four distinct memory T cell populations can be distinguished based on their functional properties. Transcriptome and proteome profiling revealed that CX3CR1 expression was superior to CD62L to resolve memory T cell functionality and allowed determination of a core signature of memory T cells with cytotoxic effector function. This identifies a CD62Lhi CX3CR1+ memory T cell population with an identical gene signature to CD62LlowCX3CR1+ effector memory T cells. In lymph nodes, this so far unrecognized CD62LhiCX3CR1+ T cell population shows a distinct migration pattern and anatomic positioning compared to CD62LhiCX3CR1neg TCM. Furthermore, CX3CR1+ memory T cells were scarce or absent during chronic HBV, HCV and HIV infection in man and chronic LCMV infection in mice confirming the value of CX3CR1+ in understanding principles of protective immune memory.
2016-06-10 | GSE63144 | GEO
Project description:Memory T cells are important for protective immunity against infectious microorganisms. Such protection is achieved by cooperative action of memory T cell populations that differ in their tissue localization and functionality. We report on the identification of the fractalkine receptor CX3CR1 as marker for stratification of memory T cells with cytotoxic effector function from those with proliferative function in both, mice and man. Based on CX3CR1 and CD62L expression levels four distinct memory T cell populations can be distinguished based on their functional properties. Transcriptome and proteome profiling revealed that CX3CR1 expression was superior to CD62L to resolve memory T cell functionality and allowed determination of a core signature of memory T cells with cytotoxic effector function. This identifies a CD62Lhi CX3CR1+ memory T cell population with an identical gene signature to CD62LlowCX3CR1+ effector memory T cells. In lymph nodes, this so far unrecognized CD62LhiCX3CR1+ T cell population shows a distinct migration pattern and anatomic positioning compared to CD62LhiCX3CR1neg TCM. Furthermore, CX3CR1+ memory T cells were scarce or absent during chronic HBV, HCV and HIV infection in man and chronic LCMV infection in mice confirming the value of CX3CR1+ in understanding principles of protective immune memory.
2016-06-10 | GSE63118 | GEO