IL-12-Independent IFN-γ Production by T Cells in Experimental Chagas’ Disease Is Mediated by IL-18

Abstract

IL-12p35-deficient (IL-12p35−/−) mice were highly susceptible to Trypanosoma cruzi infection and succumbed during acute infection, demonstrating the crucial importance of endogenous IL-12 in resistance to experimental Chagas’ disease. Delayed immune responses were observed in mutant mice, although comparable IFN-γ and TNF-α blood levels as in wild-type mice were detected 2 wk postinfection. In vivo and in vitro analysis demonstrated that T cells, but not NK cells, were recruited to infected organs. Analysis of mice double deficient in the recombinase-activating gene 2 (RAG2) and IL-12p35, as well as studies involving T cell depletion, identified CD4+ T cells as the cellular source for IL-12-independent IFN-γ production. IL-18 was induced in IL-12p35−/− mice and was responsible for IFN-γ production, as demonstrated by in vivo IL-18 neutralization studies. In conclusion, evidence is presented for an IL-12-independent IFN-γ production in experimental Chagas’ disease that is T cell and IL-18 dependent.