TRYPANOSOMA-CRUZI INFECTION IN MHC-DEFICIENT MICE - FURTHER EVIDENCE FOR THE ROLE OF BOTH CLASS-I-RESTRICTED AND CLASS-II-RESTRICTED T-CELLS IN IMMUNE RESISTANCE AND DISEASE

The role of T cell populations in immune control of Trypanosoma cruzi infection and subsequent development of disease has been examined usin g gene knockout mice deficient in the expression of either or both cla ss I and class II MHC. Mice deficient in either class I- or class II-r estricted T cell populations show a striking similarity in their morta lity rate, parasite load and tissue inflammatory response following in fection with the Brazil strain of T. cruzi. In both cases, all animals died during the acute phase of the infection with high parasitemias a nd high parasite loads in the heart and skeletal muscle, but with redu ced tissue inflammatory responses, Mice deficient in both class I and class II MHC expression demonstrated even higher numbers of circulatin g and tissue parasites, essentially non-existent tissue inflammatory r esponses, and succumbed to infection earlier than single-deficient mic e, MHC class I-deficient mice which survive into the chronic phase fol lowing infection with the M/78 or M/80 clones of T. cruzi have both re latively higher tissue parasite loads and more extensive and severe in flammatory responses than control immunocompetent mice. Immunologicall y, the acute infection in the double-deficient mice was accompanied by a marked increase in CD4(-)CD8(-) alpha beta TCR(+) cells in the sple en. Surprisingly, both class I- and class II-deficient mice produced d etectable but sub-normal levels of anti-parasite antibodies while doub le-deficient mice produced little to no detectable anti-parasite antib ody, These results establish the importance of both class I- and class Ii-restricted T cells in immune control of circulating blood stages a nd intracellular states of T: cruzi, In addition, this work reinforces the relationship between tissue parasite load and the severity of the inflammatory lesions in chronically infected animals.