Defining the early effector CD8 T cell population: plastic cells capable of populating the short-lived and memory pools. (110.11)

Abstract

Abstract Naïve antigen specific CD8 T cells expand in response to infection and can be phenotypically separated into distinct effector populations at the peak of the response, which include memory precursor effector cells (MPEC) and short-lived effector cells (SLEC). Shortly after infection, a third population called early effector cells (EEC) predominate in the antigen specific response and give rise to both the MPEC and SLEC populations. To understand if EEC populations were pre-committed to either an MPEC or SLEC fate, we purified EEC from mice infected with Listeria monocytogenes (LM) or vesicular stomatitis virus (VSV), in which the ratio of EEC/SLEC/MPEC at the peak of the response is known to be different. Transfers of sorted EEC into uninfected hosts revealed that EEC were pre-programmed to differentiate based on early signals received from the different infection settings. Additionally, gene expression analysis revealed that a subset of genes was differentially regulated between EEC derived from VSV or LM infections. Surprisingly, when these same EEC were transferred early into mismatched infected hosts, the transferred EEC were diverted from their original commitment programming. These results delineate a model of differentiation where EEC are programmed to form MPEC or SLEC, but where additional inflammatory signals can alter this program. Understanding the molecular regulation of the development of an EEC to a memory cell will facilitate rational vaccine design.