Cardiac myosin autoimmunity in acute Chagas' heart disease.
Infection with Trypanosoma 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 acute T. cruzi infection. The goal of the present study was to investigate whether cardiac autoimmunity could be observed during acute T. cruzi infection. A/J mice infected with the Brazil strain of T. cruzi for 21 days developed severe myocarditis, accompanied by humoral and cellular autoimmunity. Specifically, T. cruzi infection 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 in T. 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 upon T. cruzi infection. Therefore, humoral and cellular cardiac autoimmunity can develop during acute T. cruzi infection in the genetically susceptible host.
Leon
J S
JS
Department of Pathology and Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Godsel
L M
LM
Wang
K
K
Engman
D M
DM
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D002598:Chagas Cardiomyopathy / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology; D007111:Immunity, Cellular; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000276:immunology; D018995:Myosin Heavy Chains / Q000008:administration & dosage / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D018995:Myosin Heavy Chains