T Cell Intrinsic and Extrinsic Role of XIAP, During CD8 T Cell Response Against Intracellular Pathogens

Abstract

The magnitude and effectiveness of CD8 response against intracellular pathogens is directed by survival and apoptotic signals that govern the fate of T cells. XIAP is a bona fide endogenous inhibitor of apoptotic signals. In this thesis, I have investigated the role of XIAP at various stages of CD8 T cell response. I used both in vivo and in vitro models to show that XIAP acts in a CD8 T cell extrinsic and intrinsic manner to regulate the expansion and contraction phases of the CD8 T cell response, respectively. During the expansion phase, XIAP prevents the cell death of APCs to promote APC-T cell interaction and cytokine release, which facilitates the proliferation and survival of activated T cells. During the contraction phase, XIAP functions in a cell-intrinsic fashion to inhibit the proapoptotic signals in the activated CD8 T cells to prolong the immune response. Finally, I also demonstrate that the expression of XIAP in T cells is critical for their differentiation in to memory subsets. Overall, I present that XIAP plays a critical role in generating an effective CD8 T cell immune response.