Caveolin-1 expression in CD8 T cells positively regulates CD8 T cell function and burst size (83.15)

Abstract Caveolin-1 (Cav-1) is a molecular scaffold involved in lipid raft organization as well as protein and membrane trafficking, cytoskeletal reorganization, and regulation of signal transduction in several cell types. Despite initial reports suggesting that cav-1 is not present in lymphocytes, we have identified cav-1 expression in murine T cells by immunoblotting lysates from purified primary T cell populations. We also show that cav-1 positively regulates TCR/CD28 induced CD8 T cell activation. CD8 T cells from cav-1 knockout (KO) mice hypoproliferate and undergo 2 to 3-fold fewer cell divisions in response to 48 hrs of TCR/CD28 engagement relative to wildtype (WT) CD8 cells. Indeed, cav-1 KO CD8 T cells had a lower percentage of live cells and more cells undergoing apoptosis after 48 and 72 hrs of stimulation. To determine if cav-1 regulates CD8 T cell responsiveness in vivo, WT and cav-1 KO mice were challenged with LCMV. We found that cav-1 KO mice have both a lower percentage and absolute number of virus specific CD8 cells, providing an in vivo correlate to our findings in vitro. Further, to determine if cav-1 function is T cell intrinsic, we adoptively transferred cav-1 KO OT-1 cells into WT hosts and challenged with LM-OVA. Our findings show that cav-1 KO donor cells expanded less than WT donor cells, suggesting that cav-1 expressed by CD8 cells regulates burst size. Currently we are working to assess cav-1 subcellular localization during T cell synaptogenesis and elucidate the molecular basis of its activity. These findings identify cav-1 as a novel positive regulator of CD8 T cell activation and cell survival. T. Tomassian is predoctoral trainee recipient of the Microbial Pathogenesis Training Grant 2-T32-AI-07323.