Experimental chronic Chagas' disease myocarditis is an autoimmune disease preventable by induction of immunological tolerance to myocardial antigens.
The protozoan Trypanosoma cruzi causes chronic Chagas' disease myocarditis (CCDM) in infected mammals. The pathogenesis of CCDM, however, is still unclear. Indirect evidence for either parasite- or heart-specific immune responses playing a pathogenic role is available. In this work, the participation of autoimmunity in the development of CCDM is demonstrated in mice in which immunological tolerance to heart antigens was induced or strengthened prior to their infection by T. cruzi. Tolerance was induced by heart antigen administration in the presence of complete Freund's adjuvant and anti-CD4 antibodies. Tolerized mice developed less intense CCDM than control non-tolerized animals that had received only anti-CD4 and adjuvant. This result confirms the important notion that tolerance to self, and in particular to heart antigens, may be reinforced/induced in normal animals, and raises the possibility that analogous interventions may prevent the development of CCDM in millions of T. cruzi -infected human beings.
Pontes-de-Carvalho
Lain
L
Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, Salvador, Brazil. lain@cpunet.com.br
Santana
Cláudia C
CC
Soares
Milena B P
MB
Oliveira
Geraldo G S
GG
Cunha-Neto
Edecio
E
Ribeiro-dos-Santos
Ricardo
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001324:Autoantigens / Q000008:administration & dosage; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D015704:CD4 Antigens / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000276:immunology; D009218:Myosins / Q000008:administration & dosage / Q000276:immunology; D014349:Trypanosoma cruzi / Q000472:pathogenicity
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D015704:CD4 Antigens; D009218:Myosins