Unknown,Transcriptomics,Genomics,Proteomics

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Whole genome mRNA analysis of virus-specific CD8+ T cells expressing different levels of Id2-GFP following influenza virus infection


ABSTRACT: We speculated that distinct levels of Id2 was deterministic in the transcriptional program of antigen-specific CD8+ T cells. To test this hypothesis, we subjected DbNP366-specific effector CD8+ T cells purified according to their differential expression of Id2-GFP (Id2-GFPint and Id2-GFPhigh) to microarray analysis and compared their gene expression profiles to the differentially expressed genes identified by comparing Id2-deficient and wild-type DbNP366-specific CD8+ T cells. This analysis revealed that the transcriptional program of CD8+ T cell differentiation is exquisitely sensitive to the concentration of Id2. PR8-primed Id2gfp/gfp mice were challenged after one month with influenza intranasally HKx31 virus and analysed on day 9 for the expression of Id2-GFP in DbNP366+CD44+ CD8+ T cells. DbNP366-specific CD8+ T cells were then separated into virus-specific CD8+ T cells that expressed intermediate or high levels of GFP. Purified Id2-GFPintermediate (int) and Id2-GFPhigh DbNP366-specific CD8+ T cells were analysed by mRNA whole genome microarray. Three replicates of each group (Id2-GFPint or Id2-GFPhigh) were analysed.

ORGANISM(S): Mus musculus

SUBMITTER: Moshe Olshansky 

PROVIDER: E-GEOD-44140 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation.

Masson Frederick F   Minnich Martina M   Olshansky Moshe M   Bilic Ivan I   Mount Adele M AM   Kallies Axel A   Speed Terence P TP   Busslinger Meinrad M   Nutt Stephen L SL   Belz Gabrielle T GT  

Journal of immunology (Baltimore, Md. : 1950) 20130327 9


The transcription factor inhibitor of DNA binding (Id)2 modulates T cell fate decisions, but the molecular mechanism underpinning this regulation is unclear. In this study we show that loss of Id2 cripples effector differentiation and instead programs CD8(+) T cells to adopt a memory fate with increased Eomesodermin and Tcf7 expression. We demonstrate that Id2 restrains CD8(+) T cell memory differentiation by inhibiting E2A-mediated direct activation of Tcf7 and that Id2 expression level mirrors  ...[more]

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