Evidence that development of severe cardiomyopathy in human Chagas' disease is due to a thl-specific immune response

被引:245
作者
Gomes, JAS
Bahia-Oliveira, LMG
Rocha, MOC
Martins-Filho, OA
Gazzinelli, G
Correa-Oliveira, R
机构
[1] Fiocruz MS, Ctr Pesquisas Rene Rachou, Lab Imunol Celular & Mol, BR-30190002 Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, Fac Med, Curso Posgrad Med Trop, Belo Horizonte, MG, Brazil
[4] Univ Estadual Norte Fluminense, Lab Biol Reconhecer, Rio De Janeiro, Brazil
关键词
D O I
10.1128/IAI.71.3.1185-1193.2003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The role of interleukin 10 (IL-10) and gamma interferon (IFN-gamma) on the development of pathology in human Chagas' disease was investigated. Two categories of patients, low and high producers of IFN-gamma, 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-gamma producers. PBMC from IND patients classified as low IFN-gamma 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 (CD14(High+) cells), whereas in the CARD group, the major sources of IFN-gamma were T lymphocytes (CD3(+) CD4(+) cells). These results suggest an association between the production of IFN-gamma 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-gamma against Trypanosoma cruzi antigens favors the development of a strong Th1 response in CARD patients, which leads to progression of heart disease.
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页码:1185 / 1193
页数:9
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