title: A Human Trypanosome Suppresses CD8+ T Cell Priming by Dendritic Cells through the Induction of Immune Regulatory CD4+ Foxp3+ T Cells.
abstract: 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.
authors.affiliation: Centro de Terapia Celular e Molecular (CTCMol), Universidade Federal de São Paulo-Escola Paulista de Medicina, 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.|Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Ersching
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, São Paulo, Brazil.
authors.forename: Alexandre Salgado
authors.initials: AS
authors.lastname: Basso
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Vera Lucia Garcia
authors.initials: VL
authors.lastname: Kalich
authors.affiliation: Centro de Terapia Celular e Molecular (CTCMol), Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, São Paulo, Brazil.|Departamento de Ciências Biológicas, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Karina Ramalho
authors.initials: KR
authors.lastname: Bortoluci
authors.affiliation: Centro de Terapia Celular e Molecular (CTCMol), Universidade Federal de São Paulo-Escola Paulista de Medicina, 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.
authors.forename: Maurício M
authors.initials: MM
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology