IL-12-independent IFN-gamma production by T cells in experimental Chagas' disease is mediated by IL-18

IL-12p35-deficient (IL-12p35(-/-)) mice were highly susceptible to Trypanos oma cruzi infection and succumbed during acute infection, demonstrating the crucial importance of endogenous IL-12 in resistance to experimental Chaga s' disease. Delayed immune responses were observed in mutant mice, although comparable IFN-gamma and TNF-alpha blood levels as in wild-type mice were detected 2 wk postinfection. In vivo and in vitro analysis demonstrated tha t 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-1 2p35, as well as studies involving T cell depletion, identified CD4(+) T ce lls as the cellular source for IL-12-independent IFN-gamma production. IL-1 8 was induced in IL-12p35(-/-) mice and was responsible for IFN-gamma produ ction, as demonstrated by in vivo IL-18 neutralization studies. In conclusi on, evidence is presented for an IL-12-independent IFN-gamma production in experimental Chagas' disease that is T cell and IL-18 dependent.