Early T-bet promotes LFA1 upregulation required for CD8+ effector and memory T cell development

Abstract

The T-box transcription factor T-bet is regarded as a “master regulator” of CD4+ Th1 differentiation and IFN-γ production. However, in multiple models of infection, T-bet appears less critical for CD8+ T cell expansion and effector function. Here, we show that following vaccination with a replication-deficient strain of Toxoplasma gondii, CD8+ T cell expression of T-bet is required for optimal expansion of parasite-specific effector CD8+ T cells. Analysis of the early events associated with T cell activation reveals that the α chain of LFA1, CD11a, is a target of T-bet, and T-bet is necessary for CD8+ T cell upregulation of this integrin, which influences the initial priming of CD8+ effector T cells. We propose that the early expression of T-bet represents a T cell–intrinsic factor that optimizes T–DC interactions necessary to generate effector responses.