Bim regulates the entry of poorly functional and/or low avidity Th1 effector cells into the memory pool (85.15)

Abstract

Abstract Following the clearance of acute infection, most pathogen-specific effector T cells die, with a small minority (5-10%) surviving the contraction phase and populating the memory T cell compartment. The pro-apoptotic Bcl-2 family member Bim is central in eliminating end-stage effector T cells during contraction. We recently found that not all clones that populate the effector Th1 pool are represented in the memory phase, and failure to survive corresponded to low TCR structural and functional avidity as well as increased Bim expression. We hypothesized that Bim was required to remove unwanted low avidity Th1 responders during the transition from effector to memory. We found that Bim-deficiency rescued the survival of end-stage Th1 effector clones and allowed their entry into the memory pool. However, these cells displayed decreased primary effector function and poor recall capacity, demonstrating that while Bim played a T cell intrinsic role in the death of Th1 effector cells, its absence did not permit the rescue of effector or memory Th1 cell function. Additionally, Bim-deficient CD4+ memory T cells declined at a rate similar to wildtype memory cells, suggesting that their survival is regulated by Bim-independent factors. We propose that Bim plays a crucial role in shaping optimally functional CD4+ memory T cell repertoires by removing low avidity and/or poorly functional Th1 clones during contraction.