CD8(low) T cells expanded following acute Trypanosoma cruzi infection and benznidazole treatment are a relevant subset of IFN-γ producers

CD8 T cells are regarded as pivotal players in both immunoprotection and immunopathology following Trypanosoma cruzi infection. Previously, we demonstrated the expansion of CD8(+) T lymphocytes in the spleen of T. cruzi-infected mice under treatment with benznidazole (N-benzyl-2-nitroimidazole acetamide; Bz), a drug available for clinical therapy. This finding underlies the concept that the beneficial effects of Bz on controlling acute T. cruzi infection are related to a synergistic process between intrinsic trypanocidal effect and indirect triggering of the active immune response. In the present study, we particularly investigated the effect of Bz treatment on the CD8(+) T cell subset following T. cruzi infection. Herein we demonstrated that, during acute T. cruzi infection, Bz treatment reduces and abbreviates the parasitemia, but maintains elevated expansion of CD8(+) T cells. Within this subset, a remarkable group of CD8(low) cells was found in both Bz-treated and non-treated infected mice. In Bz-treated mice, early pathogen control paralleled the lower frequency of recently activated CD8(low) cells, as ascertained by CD69 expression. However, the CD8(low) subset sustains significant levels of CD44(high)CD62L(low) and CD62L(low)T-bet(high) effector memory T cells, in both Bz-treated and non-treated infected mice. These CD8(low) cells also comprise the main group of spontaneous interferon (IFN)-γ-producing CD8(+) T cells. Interestingly, following in vitro anti-CD3/CD28 stimulation, CD8(+) T cells from Bz-treated T. cruzi-infected mice exhibited higher frequency of IFN-γ(+) cells, which bear mostly a CD8(low) phenotype. Altogether, our results point to the marked presence of CD8(low) T cells that arise during acute T. cruzi infection, with Bz treatment promoting their significant expansion along with a potential effector program for high IFN-γ production.