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Originally published online as doi:10.1189/jlb.1006643 on January 29, 2007

Published online before print January 29, 2007
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(Journal of Leukocyte Biology. 2007;81:942-951.)
© 2007 by Society for Leukocyte Biology

The Fas death pathway controls coordinated expansions of type 1 CD8 and type 2 CD4 T cells in Trypanosoma cruzi infection

Landi V. Costilla Guillermo*, Elisabeth M. Silva*, Flávia L. Ribeiro-Gomes*, Juliana De Meis*, Wânia F. Pereira*, Hideo Yagita{dagger}, George A. DosReis* and Marcela F. Lopes*,1

* Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and
{dagger} Juntendo University School of Medicine, Tokyo, Japan

1 Correspondence: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil. E-mail: marcelal{at}biof.ufrj.br

ABSTRACT

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.

Key Words: Chagas’ disease • Th2 cytokines • apoptosis • FasL