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-β. 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. © 2016 ersching et al.