Human Gene Set: GSE15750_DAY6_VS_DAY10_TRAF6KO_EFF_CD8_TCELL_DN


Standard name GSE15750_DAY6_VS_DAY10_TRAF6KO_EFF_CD8_TCELL_DN
Systematic name M3583
Brief description Genes down-regulated in comparison of wild type CD8 effector T cells at day 6 versus those from mice defficient for TRAF6 [GeneID=7189] at day 10.
Full description or 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 ?-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.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 19494812   Authors: Pearce EL,Walsh MC,Cejas PJ,Harms GM,Shen H,Wang LS,Jones RG,Choi Y
Exact source GSE15750_1741_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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