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Int J Exp Pathol ; 83(2): 67-79, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12084043

RESUMO

CD8+ T lymphocytes are considered an important cell population involved in the control of parasitaemia and mortality after Trypanosoma cruzi infection. However, despite recent developments in this field, the mechanism whereby this control is exerted is still not completely understood. Here we have used perforin knockout (-/-) mice infected with Y strain T. cruzi in order to evaluate specifically the participation of the perforin-based cytotoxic pathway in the destruction of cardiomyocytes, cellular inflammatory infiltration, and control of parasitaemia and mortality. We observed that although parasitaemia was equivalent in perforin (+/+) and (-/-) groups, survival rate and spontaneous physical performance were significantly lower in the perforin deficient mice. The cardiac inflammatory cell infiltration, mostly composed of CD8+ cells, was more evident in perforin (-/-) mice. Ultrastructural and immunofluorescence analysis, as well as plasma creatine kinase activity, revealed cardiomyocyte damage and necrosis, more evident in perforin (-/-) mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays performed in heart samples revealed similar and modest levels of apoptosis in both perforin (+/+) and (-/-) mice. These results indicate that perforin does not play a pivotal role in the control of parasitaemia and direct lysis of cardiomyocytes, but seems to be an important molecule involved in the control of cardiac inflammation and pathology induced by a highly virulent strain of T. cruzi.


Assuntos
Cardiomiopatia Chagásica/imunologia , Glicoproteínas de Membrana/imunologia , Trypanosoma cruzi , Animais , Apoptose , Linfócitos T CD8-Positivos/imunologia , Cardiomiopatia Chagásica/patologia , Marcação In Situ das Extremidades Cortadas , Interferon gama/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/ultraestrutura , Parasitemia/imunologia , Perforina , Esforço Físico , Proteínas Citotóxicas Formadoras de Poros
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