OUTCOME OF INFECTION WITH DIFFERENT STRAINS OF TRYPANOSOMA-CRUZI IN MICE LACKING CD4 AND/OR CD8

Mice lacking CD4 and/or CD8 gene expression, generated by embryonic stem-cell technology, were used to study the role of CD4(+) and CD8(+) cells in the resistance to the acute infection with virulent (Tulahuen and RA) or mild (CA-I) strains of Trypanosoma cruzi. The presence of both CD4(+) and CD8(+) cells contributed to the survival of mice infected with T. cruzi, and each T-cell subtype was able to sustain protective functions in the absence of the other one. However, in certain host-parasite combinations, CD8(+) cell-independent mechanisms were able to control the parasite load. Moreover, CD8(-) mice chronically infected with a low virulent strain of T. cruzi were protected from an otherwise lethal challenge with the parasite. A different organ distribution of parasite nests was observed when mutant (but not wild type) animals infected with different parasite strains were compared. CD4(-) mice produced high levels of IgG antibodies against peptide antigens or a whole homogenate from the parasite after infection with CA-I strain. A dramatic enhancement of IgG1- and IgG2a-specific antibodies was observed.