ArrayExpress Uploader05677arrayexpress_sid6CD8 T cells play a crucial role in immunity to infection and cancer. They are maintained in constant numbers, but upon stimulation with...19494812E-GEOD-15750/profile/8773/arrayexpressuploader016cancercellfatty acidproteinDec.12, 2014Falsetranscription-profiling-of-mouse-cd8-t-cells-fro-2E-GEOD-15750_A-AFFY-45Transcription profiling of mouse CD8 T cells from two mouse strains (OTI-WT and OTI-TRAF6 knockout) at two timepointsNov.11, 2014CD8 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.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-15750mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-15750/samples/