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

Author(s)

Ersching, Jonatan ^{[1, 2, 3, 4]} ; Basso, Alexandre Salgado ^[2] ; Garcia Kalich, Vera Lucia ^[1] ; Bortoluci, Karina Ramalho ^{[5, 3]} ; Rodrigues, Mauricio M. ^{[2, 3]}

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Escola Paulista Med, CTCMol, Sao Paulo - Brazil

^[4] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 - USA

^[5] Univ Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLOS PATHOGENS; v. 12, n. 6 JUN 2016.
• Web of Science Citations: 4

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-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. (AU)

• FAPESP's process: 12/13032-5 - Generation and analysis of the immunogenicity of recombinant proteins based on the different allelic forms of the circumsporozoite antigen of Plasmodium vivax aiming at the development of a universal vaccine against malaria
• Grantee: Irene da Silva Soares
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/06820-4 - Characterization of antigen presenting cells capable of initiating the immune response and control the immunodominance during Trypanosoma cruzi infection
• Grantee: Maurício Martins Rodrigues
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/22514-3 - Migration study of specific T cells generated by vaccination or Trypanosoma cruzi infection
• Grantee: Jose Ronnie Carvalho de Vasconcelos
• Support Opportunities: Research Grants - Young Investigators Grants