The genetic regulation of the longevity of CD4 memory T cells. (LYM5P.660)

Abstract

Abstract We have previously reported that CD4 memory T cells enter a stage of quiescence upon resolution of infection and the consequent reduction in antigenic levels. The hyporesponsive memory T cells become responsive again upon challenge with a secondary infection, or antigen and Toll-like receptor agonists. To better understand the genetic mechanisms of the longevity of CD4 memory T cells, we performed cDNA microarray analysis of CD4 memory T cells developed after immunization with vaccinia-OVA virus using DO11.10 transgenic cells in an adoptive transfer experiment. Gene expression levels of CD4 T cells were evaluated at 9 days, 5 weeks, 6 months and 10.5 months post immunization. We repeated the experiment in DR1 transgenic mice immunized with H5N1 influenza vaccine because they have diverse polyclonal TCR repertoire and are better representative of the natural conditions. We used HLA-DR1/H5N1-HA(259-274) tetramers for staining of the antigen specific CD4 memory T cells. We found up-regulation of genes mediating DNA repair and inhibiting apoptosis, and down-regulation of glucose metabolism and up-regulation of lipid metabolism are important in longevity of CD4 memory T cells. Using FACS staining we verified several genes that were detected as significantly up-regulated by microarray experiments. These observations verified our microarray data as well as confirming our findings that long-term CD4 memory T cells are quiescent and switch from glucose to lipid metabolism.