IL-2 signals promote the differentiation of effector CD8+ T cells (132.26)

Abstract

Abstract CD8+ T cells that do not receive IL-2 signals during the primary immune response to acute infection form stable memory populations but are unable to mount successful recall responses. In this study, we found a specific defect in the differentiation and persistence of effector and effector memory CD8+ T cells in the absence of IL-2 signals during the response to lymphocytic choriomeningitis virus (LCMV) infection. Although expression levels of the effector-associated transcription factors T-bet, Eomes, and Blimp-1 did not differ significantly, unbiased analysis of gene expression by WT or IL-2Rα-deficient CTLs revealed that optimal expression of CTL effector molecules, including Granzymes and Perforin, was IL-2-dependent. The end result of CD8+ T cell activation in the absence of IL-2 was therefore decreased effector CTL activity. The defect in effector differentiation was even more profound for secondary CTL responses and in models of localized tissue-specific infection. CD8+ T cells that homed to the lung following influenza infection failed to express Granzyme B. We conclude that IL-2 provides a differentiation signal to responding CD8+ T cells that enhances access to an effector gene expression program during the primary response to infection. Furthermore, our findings suggest that IL-2 permanently imparts a gene expression imprint to CD8+ memory T cells that enables them to re-access the CTL effector program upon subsequent encounter with antigen.