PD-1 inhibits Th1 responses during cryptococcus neoformans infection (IRC2P.452)

Abstract

Abstract PD-1 is an inhibitory receptor expressed on the surface of activated T cells. PD-1 previously has been shown to play a significant role in regulating effector T cell responses against viral infections and tumors. However, its role in the control of CD4 T cell responses during infection with fungal pathogens remains poorly understood. Here we examine the role of PD-1 in regulating host responses and resistance to the opportunistic fungal pathogen Cryptococcus neoformans. We find that in wild-type mice C. neoformans elicits Th1, Th2, and Th17 responses, and PD-1 is expressed on each of these effector T cell subsets. In PD-1 deficient mice, the frequency of IFN-γ-producing and t-bet expressing CD4+ T cells were increased, while CD4+ T cells making IL-13, IL-5, and IL-4 were decreased and Th17 responses were unchanged. Also, PD-1 deficient mice show a decrease in eosinophils in the lung, and in fungal burden. These data suggest that PD-1 impairs host resistance to C. neoformans by selectively inhibiting Th1 responses. The work was supported by the NIH Intramural Research Program.