Autocrine IFN-γ Promotes Naive CD8 T Cell Differentiation and Synergizes with IFN-α To Stimulate Strong Function

Autocrine IFN-gamma signaling is important for CD4 differentiation to Th1 effector cells, but it has been unclear whether it contributes to CD8 T cell differentiation. We show in this paper that naive murine CD8 T cells rapidly and transiently produce low levels of IFN-gamma upon stimulation with Ag and B7-1, with production peaking at similar to 8 h and declining by 24 h. The autocrine IFN-gamma signals for upregulation of expression of T-bet and granzyme B and induces weak cytolytic activity and effector IFN-gamma production. IFN-alpha acts synergistically with IFN-gamma to support development of strong effector functions, whereas IL-12 induces high T-bet expression and strong function in the absence of IFN-gamma signaling. Thus, IFN-gamma is not only an important CD8 T cell effector cytokine, it is an autocrine/paracrine factor whose contributions to differentiation vary depending on whether the response is supported by IL-12 or type I IFN. The Journal of Immunology, 2012, 189: 659-668.