Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profile of murine tolerant, self-antigen specific CD8 T cells

ABSTRACT: Genomewide microarray analysis of murine tolerant, self-antigen specific CD8 T cells to identify genes and pathways underlying peripheral T cell tolerance Gene signature of tolerant CD8 T cells was compared to the signatures of naïve T cells, memory T cells, rescued T cells (=tolerant T cells undergoing homeostatic proliferation in lymphopenic, tolerogenic Alb:GAG mice), and re-tolerized T cells (=previously rescued T cells post homeostatic proliferation isolated from lymphoreplete wild-type B6 mice). Total RNA obtained from various sort-purified transgenic CD8 T cell subsets (naïve, memory, tolerant, rescued, and re-tolerized) isolated from spleens of different host mice

ORGANISM(S): Mus musculus

SUBMITTER: Andrea Schietinger

PROVIDER: E-GEOD-32025 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state.

Schietinger Andrea A Delrow Jeffrey J JJ Basom Ryan S RS Blattman Joseph N JN Greenberg Philip D PD

Science (New York, N.Y.) 20120119 6069

Tolerant self-antigen-specific CD8 T cells fail to proliferate in response to antigen, thereby preventing autoimmune disease. By using an in vivo mouse model, we show that tolerant T cells proliferate and become functional under lymphopenic conditions, even in a tolerogenic environment. However, T cell rescue is only transient, with tolerance reimposed upon lymphorepletion even in the absence of tolerogen (self-antigen), challenging the prevailing paradigm that continuous antigen exposure is cri ...[more]

PMID: 22267581

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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.

Dataset Information

Gene expression profile of murine tolerant, self-antigen specific CD8 T cells

Publications

Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state.

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