CD8 + T cells respond to signals via the T cell receptor (TCR), costimulatory molecules, and immunoregulatory cytokines by developing into diverse populations of effector and memory cells. The relative strength of phosphoinositide 3-kinase (PI3K) signaling early in the T cell response can dramatically influence downstream effector and memory T cell differentiation. We show that initial PI3K signaling during T cell activation results in up-regulation of the signaling scaffold B cell adaptor for PI3K (BCAP), which further potentiates PI3K signaling and promotes the accumulation of CD8 + T cells with a terminally differentiated effector phenotype. Accordingly, BCAP-deficient CD8 + T cells have attenuated clonal expansion and altered effector and memory T cell development following infection with Listeria monocytogenes . Thus, induction of BCAP serves as a positive feedback circuit to enhance PI3K signaling in activated CD8 + T cells, thereby acting as a molecular checkpoint regulating effector and memory T cell development.
Infectious Disease and Host Defense