Blimp-1 regulates the terminal differentiation of effector and memory CD8 T cells

In response to acute infection with intracellular pathogens, antigen-specific CD8 T cells clonally expand and undergo differentiation into effector cytotoxic lymphocytes (CTLs) that are capable of killing infected cells. The majority of effector CD8 T cells die shortly after pathogen clearance, however a small population of these cells survive as long-lived, self-renewing memory T cells. These studies have sought to determine whether Blimp-1, a transcriptional repressor that is necessary and sufficient for the terminal differentiation of multiple cell types, plays a role in effector and memory CD8 T cell differentiation. We found that Blimp-1 enhanced the formation of terminally differentiated CD8 T cells during lymphocytic choriomeningitis virus (LCMV) infection, and Blimp-1 deficiency promoted the acquisition of memory cell properties by effector cells. Blimp-1 expression was preferentially increased in terminally differentiated effector and effector memory (TEM) CD8 T cells, and gradually decayed after infection as central memory (TCM) cells developed. Blimp-1-deficient effector CD8 T cells showed some reduction in effector molecule protein expression, but primarily developed into memory precursor cells that survived better, and more rapidly acquired several TCM cell attributes, including expression of CD62L, production of IL-2 and enhanced proliferative responses. Finally, Blimp-1 appears to interact in a transcriptional network with other known regulators of CD8 T cell differentiation and its expression is positively regulated by signals that promote terminal differentiation. These results reveal a critical role for Blimp-1 in controlling terminal differentiation and suppressing memory cell developmental potential in effector CD8 T cells during viral infection.