Variations in cell-mediated immunity to Trypanosoma cruzi during experimental Chagas' disease

Abstract

Mice infected with bloodstream forms of Trypanosoma cruzi were found unable to respond significantly to subcutaneous stimulation with parasite antigens with a delayed-type hypersensitivity skin reaction during the acute phase of the disease. Consistent with this observation, peritoneal cells collected from infected mice during the acute period were unresponsive in in vitro assays for production of macrophage migration inhibitory factor. By contrast, both specific skin reactivity and significant inhibition of macrophage migration were noted during the chronic stage, i.e. when parasitaemias were on the decline or undetectable and mortality no longer occurred. Given the similarity between the kinetic changes in cell-mediated immunity monitored by in vivo tests and their in vitro correlate, the latter was used to explore the possible role of suppressor T cells in the causation of immunodeficiency recorded during the acute phase. Peritoneal cells from acutely infected animals failed to alter production of macrophage migration inhibitory factor by chronically infected mouse cells when present in mixtures at concentrations representing up to 75% of the total number of cells. Furthermore, the dilution effect of cell addition on the in vitro reaction to the trypanosomal antigens was comparable whether normal or acutely infected mouse cells were mixed with those from chronically infected animals. Removal of Lyt 2·1 bearing cells from suspensions of acutely infected mouse cells did not restore lymphocyte responsiveness to the T. cruzi antigens in the macrophage migration inhibition assay. These results show that the impairment of specific cell-mediated immunity of mice infected with T. cruzi is circumscribed to the acute phase of the disease and do not support a role for suppressor T lymphocytes in the lack of host responsiveness to the parasite's antigens.