Transcriptomics

Dataset Information

7

Transcription profiling of mouse CD8 T cells from two mouse strains (OTI-WT and OTI-TRAF6 knockout) at two timepoints


ABSTRACT: CD8 T cells play a crucial role in immunity to infection and cancer. They are maintained in constant numbers, but upon stimulation with antigen undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific populations, followed by the persistence of long-lived memory cells. Although this predictable pattern of a CD8 T cell response is well established, the underlying cellular mechanisms regulating the transition to memory remain undefined. Here we show that TRAF6, an adapter protein in the TNF-receptor (TNFR) and IL-1R/TLR superfamily, regulates CD8 T cell memory development following infection by modulating fatty acid metabolism. We show that mice with a T cell-specific deletion of TRAF6 mount robust primary CD8 T cell effector responses, but have a profound defect in their ability to generate memory. This defect is CD8 T cell intrinsic and is characterized by the disappearance of antigen-specific cells in the weeks following primary immunization. Microarray analyses revealed that TRAF6-deficient CD8 T cells from early timepoints following immunization exhibit altered expression of genes that regulate fatty acid metabolism. Consistent with this, activated CD8 T cells lacking TRAF6 are unable to upregulate mitochondrial β-oxidation in response to growth factor withdrawal in vitro. Treatment with drugs that induce fatty acid oxidation enabled CD8 T cell memory generation in the absence of TRAF6. Remarkably, these treatments also increased CD8 T cell memory in wild type mice, and consequently were able to significantly improve the efficacy of an experimental anti-cancer vaccine. Experiment Overall Design: CD8 T cells from two mouse strains (OTI-WT and OTI-TRAF6 knockout) at two timepoints (6d with 3 replicates and 10d with 5 replicates) after infection are used.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Mus musculus  

SUBMITTER: Li-San Wang  

PROVIDER: E-GEOD-15750 | ArrayExpress | 2009-06-24

SECONDARY ACCESSION(S): GSE15750PRJNA116893

REPOSITORIES: GEO, ArrayExpress

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Publications

Enhancing CD8 T-cell memory by modulating fatty acid metabolism.

Pearce Erika L EL   Walsh Matthew C MC   Cejas Pedro J PJ   Harms Gretchen M GM   Shen Hao H   Wang Li-San LS   Jones Russell G RG   Choi Yongwon Y  

Nature 20090603 7251


CD8 T cells, which have a crucial role in immunity to infection and cancer, are maintained in constant numbers, but on antigen stimulation undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific effector (T(E)) populations, followed by the persistence of long-lived memory (T(M)) cells. Although this predictable pattern of CD8 T-cell responses is well established, the underlying cellular mechanisms regulating the transit  ...[more]

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