Single cell RNA-seq profiling of CD8 T cells from elder adults
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PROVIDER: EGAS00001004255 | EGA |
REPOSITORIES: EGA
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Project description:Single cell RNA-seq profiling of ~62k purified CD8+ T cell transcriptomes, from six healthy older adult donors using 10X genomics. Cells from each donor were separated based on their IL-7R protein expression (i.e. CD8+ IL7R+ and CD8+ IL7R- T cells).
| EGAD00001006000 | EGA
Project description:CD8+ T cells are critical for the adaptive immune response to infection and tumors. Moreover, CD8+ T cell memory is important for the immune systems response to repeat infections. Here, we identify the activating transcription factor 7 interacting protein as a critical regulator of CD8+ T cell memory and effector responses. Mice with a T cell specific deletion of ATF7ip have a CD8+ T cell intrinsic enhancement of Il7r expression and Il2 expression leading to enhanced memory responses. ChIP-seq studies identified ATF7ip as an inhibitor of Il7r and Il2 gene expression through the deposition of the repressive histone mark H3K9me3 in the Il7r gene loci and Il2-Il21 intergenic region. Interestingly, ATF7ip targeted transposable elements (TE) for H3K9me3 in these regions. These results demonstrate a new epigenetic pathway by which IL7r and IL-2 production are constrained in CD8+ T cells, and this may open up new avenues for modulating their production.
2021-12-21 | GSE190624 | GEO
Project description:Using the expression of IL-18 receptor (CD218) as a surface marker, CD69+ kidney-resident CD8 T cells can be separated into two subsets. Transcriptional analysis suggests that IL-18R low subset represents the mature tissue-resident T cells
2020-03-01 | GSE111801 | GEO
Project description:CD8+ cytotoxic T lymphocytes (CTLs) play a major role in defense against intracellular pathogens, and their functions are specified by antigen recognition and innate cytokines. While effector CTLs eliminate the infection, a small population of memory cells are retained that yields more rapid and robust response upon re-infection. Antigen presenting cells secrete an array of innate cytokines including IL-12 and IFN-α after recognition of pathogens. Both IL-12 and IFN-α have been shown to act as the third signal regulating the development of CTLs. We have shown that these two cytokines have a non-redundant effect in generation of human effector CTL. IL-12 alone is sufficient for effector CTL genesis marked by IFN-γ and TNF-α production, as well as increased cytolytic activity. Even in the presence of IFN-α, IL-12 programs CTLs that express the chemokine receptor CXCR3 and effector cytokines. Using microarray analysis we have investigated how IL-12 and IFN-α differentially regulate the genetic programming pathways that give rise to effector CTLs among multiple human donors. We have also analyzed the gene expression patterns of cells sorted from healthy human peripheral blood that display surface markers of effector memory CTL (designated as ex vivo) samples. 5 healthy human donor samples were used for the in vitro cultures. For each donor the CFSE labeled cells (CD8+CD45RA+) were cultured in the presence of neutralized, IL-12, IFN-a, and IL-12+IFN-a conditions and plate-bound anti-CD3+anti-CD28 for 3.5 days. Total RNA from CFSEhi (Undiv) and CFSElo (Div) sorted cells were used for Illumina Bead Array. 4 healthy human donor samples were used for the ex vivo samples. Total RNA was collected from FACS sorted CD8+CCR7hiCXCR3lo and CD8+CCR7loCXCR3hi cells without any stimulation.
2011-09-29 | E-GEOD-27337 | biostudies-arrayexpress
Project description:Transcriptional profiling and gene expression profiling analysis of sorted CD8+IL-10+ T cells compared to CD8+IL-10- T cells using IL-10-GFP(tiger) reporter mice Two sample, CD8+IL-10+ T cells vs CD8+IL-10- T cells. Three replicate per array.
2013-06-21 | E-GEOD-37739 | biostudies-arrayexpress
Project description:Investigation of whole genome gene expression level changes in Mus musculus 3B4.15 T hybridoma cells treated with 1microMolar Dexamethasone compared to mock treated cells. Interleukin-7 receptor alpha (IL-7Rα) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7Rα expression with diverse roles in T cell biology. Here we identify the transcriptional repressor, Growth factor independent-1 (Gfi1), as a novel intermediary in glucocorticoid-induced IL-7Rα upregulation. We found Gfi1 to be a major inhibitory target of dexamethasone by microarray expression profiling of 3B4.15 T-hybridoma cells. Concordantly, retroviral transduction of Gfi1 significantly blunted IL-7Rα upregulation by dexamethasone. To further assess the role of Gfi1 in vivo, we generated bacterial artificial chromosome (BAC) transgenic mice, in which a modified Il7r locus expresses GFP to report Il7r gene transcription. By introducing this BAC reporter transgene into either Gfi1-deficient or Gfi1-transgenic mice, we document in vivo that IL-7Rα transcription is upregulated in the absence of Gfi1 and downregulated when Gfi1 is overexpressed. Strikingly, the in vivo regulatory role of Gfi1 was specific for CD8+, and not CD4+ T cells or immature thymocytes. These results identify Gfi1 as a specific transcriptional repressor of the Il7r gene in CD8 T lymphocytes in vivo. A six chip study using total RNA recovered from three separate flasks of mock treated 3B4.15 cells and three separate flasks of Dexamethasone treated 3B4.15 cells . Each chip measures the expression level of 44170 target genes
2012-07-12 | E-GEOD-39296 | biostudies-arrayexpress
Project description:Blood CD8 T cells from six healthy blood donors were treated with the TLR7 agonist imiquimod + IL-2 in T cell enriched medium overnight in vitro (the controls were incubated with T cell enriched medium + IL-2 only). After approx. 21 h the in solution digest protocol was started.
2024-04-29 | PXD038621 | Pride
Project description:To understand physiological characteristics of CD4+CD8+ Double-positive (DP)-Tfh cells, we continued to conduct comparative transcriptome analysis of tonsillar Tfh cell populations, including DP-Tfh cells and CD4+CD8- single-positive (SP)-Tfh cells as a control. Results showed that DP-Tfh cells preferentially expressed transcripts related to CTLs, such as CD8 (CD8A and CD8B), Eomes, and granzymes, suggesting a possible cytotoxic attribute of DP-Tfh cells. Th1-cell related signature genes were also presented in DP-Tfh cells and cytokines like interferon (IFN)-gamma and interleukin (IL)-10 were found to be highly presented in DP-Tfh cells rather than SP-Tfh cells. Of note, the expression profile of authentic Tfh-cell (i.e. SP-Tfh cell) related genes like IL-4, IL-21, Bcl6, and Pou2af1 seemed to be shared with DP-Tfh cells.
2022-08-10 | GSE202616 | GEO
Project description:IL-10 is an anti-inflammatory cytokine that has been shown to be produced by antigen-specific CD8 T cells at the peak of viral encephalitis. We found that IL-10+CD8 T cells are more activated and cytolytic than IL-10-CD8 T cells. We used microarrays to detect gene expression changes in directly ex vivo sorted CNS IL-10+ and IL-10- CD8 T cells from a neurotropic J2.2-V-1-infected mouse. C57Bl/6 Vert-X (IL-10-eGFP) mice were infected intracranially with 500 PFU J2.2-V-1 virus and seven days later their brain lymphocytes from three mice were pooled and then isolated and negatively selected for CD8 T cells. The CD8 pooled brain lymphocytes were then sorted for IL-10+ and IL-10- CD8 T lymphocytes using GFP as a marker from the same samples. This was performed three times to obtain six samples total. RNA was extracted and hybridized to GeneChip Mouse GENE 1.0 ST arrays (Affymetrix).
2010-12-07 | E-GEOD-25846 | biostudies-arrayexpress
Project description:CD8+ T-cells provide robust anti-viral immunity, yet how epitope-specific T-cells evolve across the human lifespan is unknown. We defined CD8+ T-cell immunity directed at the prominent influenza epitope, HLA-A*02:01-M158-66 (A2/M158) across four age groups (newborns, children, adults and elderly) ex vivo at phenotypic, single cell sequence (transcriptomic), clonal and functional levels. We identified a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resembled those observed in newborns and children, despite being clonally-different. However, only child- and adult-derived A2/M158+CD8+ T-cells had the potential to differentiate into highly cytotoxic epitope-specific CD8+ T-cells, which was linked to highly functional public TCRab-signatures. Suboptimal TCRab-signatures detected in older adults led to poorer proliferation, polyfunctionality, avidity and recognition of peptide mutants, although displayed no signs of exhaustion. Our study suggests that priming T-cells at different stages of life might greatly affect CD8+ T-cell responses towards viral infections.
2023-08-16 | GSE237817 | GEO