Chagas' disease and the autoimmunity hypothesis

The notion that the pathology of Chagas' disease has an autoimmune componen t was initially based on the finding of circulating antibodies binding hear t tissue antigens in patients and mice chronically infected with Trypanosom a cruzi. Later; T lymphocytes reactive with heart or nerve tissue antigens were found in chagasic mice and patients, extending the concept to include cell-mediated immunity. However; there is dir;agreement about whether the o bserved immunologic autoreactivities are triggered by T. cruzi epitopes and then affect host tissue antigens by virtue of molecular mimicry or are eli cited by host antigens exposed to lymphocytes after tissue damage caused by the parasite. There is also disagreement about the relevance of immunologi c autoreactivities to the pathogenesis of Chagas' disease because of the th e lack of reproducibility of some key reports supporting the autoimmunity h ypothesis, conflicting data from independent laboratories, conclusions inva lidated by advances in our understanding of the immunologic mechanisms unde rlying cell lysis, and, last but not least, a lack of direct, incontroverti ble evidence that cross-reacting antibodies ol autoreactive cells mediate t he typical pathologic changes associated with human Chagas' disease. The da ta and views backing and questioning the autoimmunity hypothesis for Chagas ' disease are summarized in this review.