Plasticity and commitment of memory CD8+ T cell progenitors early after infection (46.13)

Abstract

Abstract Naïve antigen specific CD8+ T cells expand in response to antigenic stimulation to form a large effector T cell population. Following expansion, the majority of the antigen specific CD8+ T cells die, leaving behind a memory population capable of protecting the host. CD8+ T cell memory formation has been extensively studied, but little is understood about the early events in memory commitment. At the peak of the T cell response, effector T cells can be separated using the markers CD127 (IL-7Rα) and KLRG1. Memory precursor effector cells (MPECs) express CD127 while short-lived effector cells (SLECs) express KLRG1. CD8+ T cells lacking expression of both markers are called early effector cells (EECs) and can give rise to both the MPECs and SLECs. To understand if EEC populations are committed to either an MPEC or SLEC fate prior to differentiation, we used EECs generated from Listeria monocytogenes and vesicular stomatitis virus infections, where the ratio of SLECs/MPECs at the peak of the T cell response is known to be different. EECs were sorted and transferred into infection-matched or mismatched hosts at various days post infection. As late as 7 days post-infection the EECs were not committed to an MPEC or SLEC fate and could be driven in either direction based on the inflammatory environment of the host. Based on these results we conclude that commitment of a CD8 T cell toward a memory lineage does not occur until after CD127 expression has been established.