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

PLoS Pathogens

Jonatan Ersching¹  Vera Lucia Garcia Kalich²  Maurício M. Rodrigues²  Karina Ramalho Bortoluci³  Alexandre Salgado Basso³ 

[1] Centro de Terapia Celular e Molecular (CTCMol), Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, São Paulo, Brazil;Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brazil;Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, São Paulo, Brazil

关键词: T cells;    Cytotoxic T cells;    Trypanosoma cruzi;    Cell staining;    Cytokines;    Immune response;    Regulatory T cells;    Spleen;   

DOI  :  10.1371/journal.ppat.1005698

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY