A Human Trypanosome Suppresses CD8+ T Cell Priming by Dendritic Cells through the Induction of Immune Regulatory CD4+ Foxp3+ T Cells

Although CD4(+) Foxp3(+) T cells are largely described in the regulation of CD4(+) T cell responses, their role in the suppression of CD8(+) T cell priming is much less clear. Because the induction of CD8(+) T cells during experimental infection with Trypanosoma cruzi is remarkably delayed and suboptimal, we raised the hypothesis that this protozoan parasite actively induces the regulation of CD8(+) T cell priming. Using an in vivo assay that eliminated multiple variables associated with antigen processing and dendritic cell activation, we found that injection of bone marrow-derived dendritic cells exposed to T. cruzi induced regulatory CD4(+) Foxp3(+) T cells that suppressed the priming of transgenic CD8(+) T cells by peptide-loaded BMDC. This newly described suppressive effect on CD8(+) T cell priming was independent of IL-10, but partially dependent on CTLA-4 and TGF-beta. Accordingly, depletion of Foxp3(+) cells in mice infected with T. cruzi enhanced the response of epitope-specific CD8(+) T cells. Altogether, our data uncover a mechanism by which T. cruzi suppresses CD8(+) T cell responses, an event related to the establishment of chronic infections.