Increased susceptibility of Fas ligand-deficient gld mice to Trypanosoma cruzi infection due to a Th2-biased host immune response

Infection of BALB/c mice with Trypanosoma cruzi resulted in up-regulated ex pression of Fas and Fas ligand (FasL) mRNA by splenic CD4(+) T cells, activ ation-induced CD4(+) T cell death (AICD), and in Fas:FasL-mediated cytotoxi city. When CD4(+) T cells from infected mice were co-cultured with T. cruzi -infected macrophages, onset of AICD exacerbated parasite replication. CD4( +) T cells from T. cruzi-infected FasL-deficient BALB gld/gld mice had no d etectable AICD in vitro and their activation with anti-TCR did not exacerba te T. cruzi replication in macrophages. However, infection of BALE gld/gld mice with T. cruzi resulted in higher and more prolonged parasitemia, compa red to wild-type mice. Secretion of Th2 cytokines IL-10 and IL-4 by CD4(+) T cells from infected gld mice was markedly increased, compared to controls . In addition, in vivo injection of anti-IL-4 mAb, but not of an isotype co ntrol mAb, reduced parasitemia in both gld and wild-type mice. These result s indicate that, besides controlling CD4(+) T cell AICD and parasite replic ation in vitro, an intact Fas:FasL pathway also controls the host cytokine response to T. cruzi infection in vivo, being required to prevent an exacer bated Th2-type immune response to the parasite.