[Immunologic studies on a murine model of Chagas disease]

In an experimental model, T. cruzi infected mice develop a chronic myocarditis with mononuclear infiltrates rich in CD4 lymphocytes and macrophages with scarce B and CD8 lymphocytes. The infected mice present in the spleen lymphocytes cytotoxic for adult syngeneic cardiocytes and in their sera antibodies able to induce antibody-dependent cytotoxicity (ADCC) against adult cardiocytes in a syngeneic system with spleen lymphocytes as effector cells. Myocarditis with electrocardiographic alterations was induced in naive recipients by transfer of lymphocytes from chagasic syngeneic mice. Immunization with subcellular fractions of T. cruzi led to a chronic myocarditis similar to that observed in infected animals; mice with autoimmune myocarditis induced by immunization with heart antigens developed antibodies which bind to T. cruzi epitopes. Glucocorticoids administered with trypanocidal drugs dramatically reduce the electrocardiographic alterations and to a lesser extent the myocarditis. Parasitological "cure" by treatment with trypanocidal drugs led to loss of the premunition state associated with the disappearance of antibodies able to induce complement-mediated lysis or ADCC against circulating forms of T. cruzi. However, both resistance against a challenge with a small number of parasites and cell-mediated anti T. cruzi immunity persisted. Our studies suggest that more than a single immunopathological mechanism is involved since anti-heart T cell cytotoxicity delayed type hypersensitivity and antiheart ADCC have been observed in chronically infected mice; this could be due to the existence of epitopes shared by the heart and the parasite.