The IL-27R (WSX-1) Is Required to Suppress T Cell Hyperactivity during Infection

AbstractAlthough recent studies have described IL-27 and its receptor, WSX-1, as promoters of Th1 differentiation in naive CD4+ T cells, the data presented here indicate that signaling through this receptor is involved in limiting the intensity and duration of T cell activity. When WSX-1-deficient mice are infected with the intracellular pathogen Toxoplasma gondii, they establish protective T cell responses, characterized by production of inflammatory cytokines and control of parasite replication. However, infected WSX-1−/− mice are unable to downregulate these protective responses, and develop a lethal, T cell-mediated inflammatory disease. This pathology was characterized by the excessive production of IFN-γ, persistence of highly activated T cells, and enhanced T cell proliferation in vivo. Together, these findings demonstrate that WSX-1 is not required for the generation of IFN-γ−mediated immunity to this parasitic infection and identify a novel function for this receptor as a potent antagonist of T cell-mediated, immune hyperactivity