The Fas death pathway controls coordinated expansions of type 1 CD8 and type 2 CD4 T cells inTrypanosoma cruziinfection

Autor: Marcela F. Lopes, Flávia L. Ribeiro-Gomes, Hideo Yagita, Elisabeth M. Silva, Juliana de Meis, Landi V. C. Guillermo, George A. DosReis, Wânia F. Pereira
Rok vydání: 2007
Předmět:
Zdroj: Journal of Leukocyte Biology. 81:942-951
ISSN: 1938-3673
0741-5400
DOI: 10.1189/jlb.1006643
Popis: We investigated the role of the Fas ligand (FasL)/Fas death pathway on apoptosis and cytokine production by T cells in Trypanosoma cruzi infection. Anti-FasL, but not anti-TNF-α or anti-TRAIL, blocked activation-induced cell death of CD8 T cells and increased secretion of IL-10 and IL-4 by CD4 T cells from T. cruzi-infected mice. CD4 and CD8 T cells up-regulated Fas/FasL expression during T. cruzi infection. However, Fas expression increased earlier in CD8 T cells, and a higher proportion of CD8 T cells was activated and expressed IFN-γ compared with CD4 T cells. Injection of anti-FasL in infected mice reduced parasitemia and CD8 T cell apoptosis and increased the ratio of CD8:CD4 T cells recovered from spleen and peritoneum. FasL blockade increased the number of activated T cells, enhanced NO production, and reduced parasite loads in peritoneal macrophages. Injection of anti-FasL increased IFN-γ secretion by splenocytes responding to T. cruzi antigens but also exacerbated production of type 2 cytokines IL-10 and IL-4 at a late stage of acute infection. These results indicate that the FasL/Fas death pathway regulates apoptosis and coordinated cytokine responses by type 1 CD8 and type 2 CD4 T cells in T. cruzi infection.
Databáze: OpenAIRE