Inhibition of caspase-8 activity reduces IFN-gamma expression by T cells from Leishmania major infection

• Autor(a) principal: Pereira,Wânia F.
• Data de Publicação: 2008
• Outros Autores: Guillermo,Landi V.C., Ribeiro-Gomes,Flávia L., Lopes,Marcela F.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Anais da Academia Brasileira de Ciências (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652008000100008
• topic: apoptosis; caspase-8; CD8 T cells; IFN-gamma; Leishmaniasis

Following infection with Leishmania major, T cell activation and apoptosis can be detected in draining lymph nodes of C57BL/6-infected mice. We investigated the mechanisms involved in apoptosis and cytokine expression following Tcellactivation. After two weeks of infection, apoptotic T cells were not detected in draining lymph nodes but activation with anti-CD3 induced apoptosis in both CD4 and CD8 T cells. Treatment with anti-FasLigand, caspase-8 or caspase- 9 inhibitors did not block activation-induced T-cell death. We also investigated whether the blockade of caspase-8 activity would affect the expression of type-1 or type-2 cytokines. At early stages of infection, both CD4 and CD8 T cells expressed IFN-gamma upon activation. Treatment with the caspase-8 inhibitor zIETD-fmk (benzyl-oxycarbonyl-Ile- Glu(OMe)-Thr-Asp(OMe)-fluoromethyl ketone) reduced the proportion of CD8 T cells and IFN-gamma expression in both CD4 and CD8T cells. We conclude that a non apoptotic role of caspase-8 activity may be required for T cell-mediated type-1 responses during L. major infection.