Epigenetics of CD8 T cell differentiation and aging
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ABSTRACT:
PROVIDER: PRJNA338720 | ENA |
REPOSITORIES: ENA
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Project description:<p>The efficacy of the adaptive immune response declines dramatically with age, but the cell-intrinsic mechanisms driving the changes characteristic of immune aging in humans remain poorly understood. One hallmark of immune aging is the loss of self-renewing naive cells and the accumulation of differentiated but dysfunctional cells within the CD8 T cell compartment. Using ATAC-seq, we first inferred the transcription factor binding activities that maintain the naive and central and effector memory CD8 T cell states in young adults. Integrating our results with RNA-seq, we determined that BATF, ETS1, Eomes, and Sp1 govern transcription networks associated with specific CD8 T cell subset properties, including activation and proliferative potential. Extending our analysis to aged humans, we found that the differences between memory and naive CD8 T cells were largely preserved across age, but that naive and central memory cells from older individuals exhibited a shift toward a more differentiated pattern of chromatin openness. Additionally, aged naive cells displayed a loss in chromatin openness at gene promoters, a phenomenon that appears to be due largely to a loss in binding by NRF1, leading to a marked drop-off in the ability of the naive cell to initiate transcription of mitochondrial genes. Our findings identify BATF- and NRF1-driven gene regulation as targets for delaying CD8 T cell aging and restoring T cell function.</p>
| phs001187 | dbGaP
Project description:Epigenetics of CD8 T cell differentiation and aging
| PRJNA338721 | ENA
Project description:This phase I pilot trial studies the side effects of cluster of differentiation 8 (CD8)+ T cells in treating patients with gastrointestinal tumors that have spread to other places in the body. Tumor cells and blood are used to help create an adoptive T cell therapy, such as CD8+ T cell therapy, that is individually designed for a patient and may help doctors learn more about genetic changes in the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CD8+ T cell therapy and pembrolizumab may work better in treating patients with gastrointestinal tumors.
| 2214011 | ecrin-mdr-crc
Project description:In response to acute infection CD8 T cells differentiate into effector cells capable of clearing the antigen. While the transcriptional and functional changes have previously been studied little is known of the epigenetic modifications that accompany this differentiation process. To gain insights into CD8 T cell effector differentiation and the role of epigenetics, we mapped DNA methylation by MeDIP-seq in naive CD8 T cells and day 8 effector CD8 T cells that are induced following an acute infection. We identified hundreds of thousands of differentially methylated regions (DMRs). Promoter DNA methylation inversely correlated with gene expression and DMRs were enriched for functional transcription factor binding sites. These data indicated that DNA methylation is dynamic during CD8 T cell differentiation and provide a map of possible regulatory regions important in this process. Examination of DNA methylation during CD8 T cell differentiation from naïve to day 8 effectors following acute infection
2013-08-18 | E-GEOD-44638 | biostudies-arrayexpress
Project description:Recently, the bone marrow (BM) has been shown to play a key role in regulating the survival and function of memory T cells. However, the impact of aging on these processes has not yet been studied. We demonstrate that the number of CD4+ and CD8+ T cells in the BM is maintained during aging. However, the composition of the T cell pool in the aged BM is altered with a decline of naïve and an increase in effector-memory T cells. In contrast to the peripheral blood (PB), a highly activated CD8+CD28– T cell population, which lacks the late differentiation marker CD57, accumulates in the BM of elderly persons. IL-6 and IL-15, which are both increased in the aged BM, efficiently induce the activation, proliferation and differentiation of CD8+ T cell in vitro, highlighting a role of these cytokines in the age-dependent accumulation of highly activated CD8+CD28– T cells in the BM. Yet, these age-related changes do not impair the maintenance of a high number of polyfunctional memory CD4+ and CD8+ T cells in the BM of elderly persons. In summary, aging leads to the accumulation of a highly activated CD8+CD28– T cell population in the BM, which is driven by the age-related increase of IL-6 and IL-15. Despite these changes, the aged BM is a rich source of polyfunctional memory T cells and may thus represent an important line of defense to fight recurrent infections in old age. A total of 4 samples (bone marrow mononuclear cells) were analyzed (2 young and 2 elderly persons)
2011-10-11 | E-GEOD-32725 | biostudies-arrayexpress
Project description:In response to acute infection CD8 T cells differentiate into effector cells capable of clearing the antigen. While the transcriptional and functional changes have previously been studied little is known of the epigenetic modifications that accompany this differentiation process. To gain insights into CD8 T cell effector differentiation and the role of epigenetics, we mapped DNA methylation by MeDIP-seq in naive CD8 T cells and day 8 effector CD8 T cells that are induced following an acute infection. We identified hundreds of thousands of differentially methylated regions (DMRs). Promoter DNA methylation inversely correlated with gene expression and DMRs were enriched for functional transcription factor binding sites. These data indicated that DNA methylation is dynamic during CD8 T cell differentiation and provide a map of possible regulatory regions important in this process.
2013-08-18 | GSE44638 | GEO
Project description:Constitutive CD8 expression drives innate CD8+ T cell differentiation via induction of iNKT2 subset
| PRJNA545741 | ENA
Project description:T cells from several blood donors were separated in populations corresponding to CD8+ CD28+ and CD8+ CD28- surface markers. Total RNA extracts from cells were hybridized to MRC LNA microarray. Contrasts of interest were CD8CD28- minus CD8CD28+ (replicative aging) and CD8CD28+ (old donors) minus CD8CD28+ (young donors), which corresponds to chronological aging.
2010-04-19 | E-MEXP-2398 | biostudies-arrayexpress
Project description:Constitutive CD8 expression drives innate CD8+ T cell differentiation via induction of iNKT2 subset.
2019-06-01 | GSE132059 | GEO
Project description:Batf-mediated Epigenetic Control of Effector CD8+ T Cell Differentiation
| PRJNA791324 | ENA