Heart-infiltrating and peripheral T cells in the pathogenesis of human Chagas' disease cardiomyopathy.
Heart tissue destruction in chronic Chagas' disease cardiomyopathy (CCC), occurring in 30% of individuals chronically infected by the protozoan parasite Trypanosoma cruzi, may be caused by autoimmune recognition of patients' heart tissue by a T cell rich inflammatory infiltrate. Recently, our group demonstrated that T cells infiltrating the heart of CCC patients crossreactively recognize cardiac myosin heavy chain and tandemly repetitive T. cruzi antigen B13, and possess an inflammatory T1-type cytokine profile. Susceptibility factors leading 30% of infected patients to develop CCC, while the rest of the patients remain largely asymptomatic (ASY), are still obscure. We compared immunological phenotypes of CCC and ASY patients, who have distinct clinical outcomes despite bearing a similar chronic T. cruzi infection. Preliminary observations indicate that PBMC from CCC patients recognize a set of B13 and cardiac myosin epitopes distinct from that recognized by ASY patients. Moreover, the IFN-gamma response of CCC patients is more intense than that of ASY, both at qualitative and quantitative levels. Taken together, results suggest that heart damage in Chagas' disease cardiomyopathy may be secondary to inflammatory cytokines and a delayed-type hypersensitivity process started and/or maintained by heart-crossreactive T cells. Furthermore, the distinct recognition repertoire and the high frequency of IFN-gamma producing among CCC patients could be important factors leading to the differential development of CCC among T. cruzi infected individuals.
Cunha-Neto
E
E
Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, SP, Brazil. edecunha@usp.br
Kalil
J
J
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines