Cardiac Myosin Autoimmunity in Acute Chagas' Heart Disease

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Abstract
Infection withTrypanosoma cruzi, the agent of Chagas' disease, may induce antibodies and T cells reactive with self antigens (autoimmunity). Because autoimmunity is generally thought to develop during the chronic phase of infection, one hypothesis is that autoimmunity develops only after long-term, low-level stimulation of self-reactive cells. However, preliminary reports suggest that autoimmunity may begin during acuteT. cruziinfection. The goal of the present study was to investigate whether cardiac autoimmunity could be observed during acuteT. cruziinfection. A/J mice infected with the Brazil strain ofT. cruzifor 21 days developed severe myocarditis, accompanied by humoral and cellular autoimmunity. Specifically,T. cruziinfection induced immunoglobulin G (IgG) autoantibodies and delayed type hypersensitivity (DTH) to cardiac myosin. This autoimmunity resembles that which develops in A/J mice immunized with myosin in complete Freund's adjuvant in that myosin-specific antibodies and DTH responses both develop by 21 days postinfection or postimmunization. While the levels of myosin IgG inT. cruzi-infected mice were slightly lower than those in myosin-immunized mice, the magnitude of myosin DTH in the two groups was statistically equivalent. In contrast, C57BL/6 mice, which are resistant to myosin-induced myocarditis and its associated autoimmunity, developed undetectable or low levels of myosin IgG and did not exhibit myosin DTH or myocarditis uponT. cruziinfection. Therefore, humoral and cellular cardiac autoimmunity can develop during acuteT. cruziinfection in the genetically susceptible host.