Early T-bet promotes LFA1 upregulation required for CD8+ effector and memory T cell development
Gretchen Harms Pritchard, Anthony T. Phan, David A. Christian, Trevor J. Blain, Qun Fang, John L. Johnson, Nathan H. Roy, Lindsey A. Shallberg, Ross M. Kedl, Christopher A. Hunter
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.