RESUMO
We have previously reported that heart lesions in patients with chronic cardiac Chagas' disease are composed predominantly of granzyme A+, cytolytic CD8+ T lymphocytes. We now pursue this study in the immunopathology of chronic chagasic cardiomyopathy by investigation of the expression of HLA antigens, and adhesion molecules in the hearts of seven chagasic patients with cardiac disease, two asymptomatic chagasic patients, and seven normal controls. Comparative immunohistochemical analyses show that HLA-ABC antigen expression is enhanced on the myocardial cells of chagasic patients with chronic cardiomyopathy, suggesting a possible role for these cells as targets for the CD8+ cytolytic lymphocytes dominant in these lesions. The HLA-DR antigens are not observed on myocardial cells, but are consistently upregulated on the endothelial cells in the hearts of patients with chronic chagasic cardiomyopathy. Intercellular adhesion molecule is expressed by endothelial cells of both chagasic and nonchagasic individuals, but E-selectin was detected only on vessels of hearts from chagasic patients who had chronic cardiomyopathy. Most of the lymphocytes in these lesions express lymphocyte function antigen-1 (LFA-1), CD44, and very late antigen-4, and a few display weak expression of LFA-3. We propose that the expression of these adhesion molecules and major histocompatibility complex antigens by endothelial cells, myocardial cells, and lymphoid cells in these lesions contribute to the pathogenesis of chronic chagasic cardiomyopathy.
Assuntos
Moléculas de Adesão Celular/análise , Cardiomiopatia Chagásica/imunologia , Antígenos HLA/análise , Miocárdio/imunologia , Adulto , Idoso , Cardiomiopatia Chagásica/patologia , Doença Crônica , Selectina E , Feminino , Antígenos HLA-DR/análise , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular , Antígeno-1 Associado à Função Linfocitária/análise , Masculino , Pessoa de Meia-Idade , Miocárdio/patologiaRESUMO
The inflammatory infiltrates in the heart lesions of chronic chagasic cardiomyopathy are composed predominantly of small lymphocytes with admixed macrophages, plasma cells, and segmented leukocytes. The phenotypes of the lymphoid cells in these infiltrates of human Chagas' disease have not been previously detailed. We used a panel of monoclonal and polyclonal antibodies to immunohistochemically characterize the inflammatory cells in frozen and fixed cardiac tissues from autopsied patients with severe chronic chagasic cardiomyopathy. In all cases, the inflammatory lesions were dominated by CD8+ lymphocytes, many of which expressed granzyme A. A few macrophage-like cells that expressed tumor necrosis factor-alpha were observed in each case. Relatively few natural killer cells or B lymphocytes were found in the lesions. These findings in human chagasic lesions are compatible with concepts that involve cytolysis and fibrosis, and new experimental findings that emphasize potential roles for CD8+ T cells in Chagas' disease.