Effects of nitric oxide (NO) on T cell responses in a murine chronic infection with Trypanosoma cruzi.

NOELIA GROSSO; ALBAREDA M C; ESTEVA MÓNICA; LOPEZ ALARCÓN M; LAUCELLA S; FICHERA L

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2012

We have previously shown an inhibitory effect of NO on the degranulation capacity of CD8+ T cells in a murine chronic infection with Trypanosoma cruzi. Herein, the action of NO on the T. cruzi-specific apoptotic and secretory capacity of cytokines by T cells in C3H/HeN mice infected with T. cruzi Sylvio-X10/4 was evaluated. In addition, the degranulation capacity of CD8+ T cells in relation to NO levels was investigated. Splenocytes and cardiac infiltrates were co-cultured with autologous monocytes in the presence of an NO donor (SNAP), NO inhibitor (L-NAME) or controls with media. The frequencies of CD8+CD107+ and CD8+Anexin+ T cells were measured by flow cytometry, while the levels of IFN-γ and IL-2 were determined by a capture ELISA assay. An inverse significant correlation between NO levels and the frequencies of CD8+CD107+ T cells specific for T. cruzi was found (slope=-3.99; p=0.02). T. cruzi-infected splenocytes produced high levels of IFN-γ, that was inhibited by SNAP and reverted by L-NAME addition. Apoptosis of CD8+ T cells was low and was not modified by SNAP or L-NAME. IFN-γ and IL-2 were secreted by cardiac infiltrates from chronically infected mice. The addition of SNAP induced a decrease in the levels of both cytokines, which was reverted by L-NAME. These findings support that NO might inhibit T. cruzi specific Th1 responses in chronically infected mice.