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Infection and Immunity, March 2003, p. 1185-1193, Vol. 71, No. 3
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.3.1185-1193.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Evidence that Development of Severe Cardiomyopathy in Human Chagas' Disease Is Due to a Th1-Specific Immune Response
J. A. S. Gomes,1,2 L. M. G. Bahia-Oliveira,3 M. O. C. Rocha,4 O. A. Martins-Filho,2 G. Gazzinelli,2 and R. Correa-Oliveira2*
Departamento de Bioquímica e Imunologia,1
Faculdade de Medicina, Curso de Pós-graduação em Medicina Tropical, Universidade Federal de Minas Gerais,4
Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Minas Gerais,2
Laboratório de Biologia do Reconhecer, Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, Rio de Janeiro, Brazil3
Received 11 June 2002/
Returned for modification 27 August 2002/
Accepted 3 December 2002
The role of interleukin 10 (IL-10) and gamma interferon (IFN-
) on the development of pathology in human Chagas' disease was investigated. Two categories of patients, low and high producers of IFN-
, were identified based on the levels of secretion of this cytokine in the supernatant of peripheral blood mononuclear cell (PBMC) cultures. Eighty-three percent of the patients presenting with cardiac disease (CARD) of different degrees and 59% of the patients with the indeterminate form of disease (IND) were identified as high IFN-
producers. PBMC from IND patients classified as low IFN-
producers secreted significantly higher amounts of IL-10 than did those from other groups. Flow cytometry analysis demonstrated that in PBMC from the IND group, the majority of the IL-10-producing cells were monocytes (CD14High+ cells), whereas in the CARD group, the major sources of IFN-
were T lymphocytes (CD3+ CD4+ cells). These results suggest an association between the production of IFN-
by CD3+ CD4+ cells and morbidity in Chagas' disease, whereas the production of IL-10 by macrophages/monocytes leads to regulation of the immune response in IND patients. We hypothesize that an exacerbated production of IFN-
against Trypanosoma cruzi antigens favors the development of a strong Th1 response in CARD patients, which leads to progression of heart disease.
* Corresponding author. Mailing address: Centro de Pesquisas René Rachou/FIOCRUZ, Laboratório de Imunologia Celular e Molecular, Av. Augusto de Lima 1715, 30190-002, Belo Horizonte, MG, Brazil. Phone: 55 31 32953566. Fax: 55 31 32953115. E-mail:
correa{at}cpqrr.fiocruz.br.
Editor: J. M. Mansfield
Infection and Immunity, March 2003, p. 1185-1193, Vol. 71, No. 3
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.3.1185-1193.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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