The Fas death pathway controls coordinated expansions of type 1 CD8 and type 2 CD4 T cells in Trypanosoma cruzi infection.
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-alpha 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-gamma 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-gamma 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.
Guillermo
Landi V Costilla
LV
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
Silva
Elisabeth M
EM
Ribeiro-Gomes
Flávia L
FL
De Meis
Juliana
J
Pereira
Wânia F
WF
Yagita
Hideo
H
DosReis
George A
GA
Lopes
Marcela F
MF
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D049109:Cell Proliferation; D014355:Chagas Disease / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D015398:Signal Transduction; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
D016207:Cytokines; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; D019014:fas Receptor