Late antigen recognition at the memory checkpoint is necessary for CD4+ T cell memory formation. (IRC9P.708)

Abstract

Abstract During the contraction phase of an influenza immune response, the majority of responding T cells undergo Bim-driven apoptosis leaving a small, heterogeneous population of T cells that will survive to form memory. The regulation of this process is poorly understood. Recently, our lab defined a “memory checkpoint” during which highly differentiated effector CD4+ T cells require autocrine IL-2 immediately preceding contraction to become memory. To determine whether antigen recognition is required for IL-2 production during the memory checkpoint, we developed an adoptive transfer model to modulate antigen. Donor CD4+ effectors transferred to hosts without antigen underwent immediate cell death and failed to form memory, suggesting that antigen recognition is indeed the key event at this checkpoint. The ex vivo evaluation of CD4+ effector cells at the memory checkpoint revealed that both co-stimulation and IL-2 signaling contribute to survival. TCR stimulation during the memory checkpoint resulted in higher sustained expression of memory markers CD127 and CXCR3. The survival to memory is mediated in part by a sustained reduction in Bim expression, as the requirement for late antigen interactions was eliminated in Bim heterozygous CD4+ T cells. These findings demonstrate that effectors generated by influenza must recognize antigen at the memory checkpoint to become memory.