Bim-mediated selection of efficient CD8 T cell memory following viral infection 4695

Abstract Description Adaptive immunity is defined by the ability to form a functional “memory” of an antigenic encounter, and this provides the basis for successful responses to vaccines and infections. For CD8 T cells (and other lymphocytes), memory formation is preceded by the elimination of effector cells through both extrinsic and intrinsic apoptosis. The more we understand this process of contraction, the more effectively it can be therapeutically manipulated. The objective of this study, therefore, is to examine the relationship between T cell contraction and memory formation in vivo. Using bone marrow chimeras and adoptive transfers to restrict genetic knockouts to the immune system and CD8 T cells respectively, we describe the role of Bid and Bim in the formation of CD8 T cell memory during primary and recall responses to systemic lymphocytic choriomeningitis virus (LCMV) and mucosal influenza virus (IAV) infections. We find that Bim-mediated apoptosis plays a more prominent role in effector contraction than Bid-mediated apoptosis and Bim deficiency leads to an inflation of antigen experienced (CD44hi) cells after acute infections. Surprisingly, however, his larger population of CD8 T cells does not translate into a more effective memory pool. Although displaying phenotypic markers characteristic of memory, Bim-deficient CD8 T Cells lack the functional qualities of memory cells and display signs of metabolic dysregulation. Thus, Bim is necessary for the selection of high-quality memory. Funding Sources Supported by ALSAC. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)