Standard name GSE15750_WT_VS_TRAF6KO_DAY10_EFF_CD8_TCELL_UP
Systematic name M3573
Brief description Genes up-regulated in comparison of wild type CD8 effector T cells at day 10 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 gene sets
      IMMUNESIGDB: ImmuneSigDB gene sets
Source publication Pubmed 19494812   Authors: Pearce EL,Walsh MC,Cejas PJ,Harms GM,Shen H,Wang LS,Jones RG,Choi Y.
Exact source GSE15750_1739_200_UP
Related gene sets (show 7 additional gene sets from the source publication)

(show 14 gene sets from the same authors)
External links  
Filtered by similarity
Organism Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
Source platform HUMAN_GENE_SYMBOL
Dataset references (show 1 datasets)
Download gene set format: grp | text | gmt | gmx | xml
Compute overlaps (show collections to investigate for overlap with this gene set)
Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 200 genes
Gene families Categorize these 200 genes by gene family
Show members (show 200 members mapped to 200 genes)
Version history 7.3: Moved to ImmuneSigDB sub-collection.

See MSigDB license terms here. Please note that certain gene sets have special access terms.