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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 5
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
Total Affiliations: 5
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: 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 type: 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 type: Research Grants - Young Investigators Grants
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 type: Research Projects - Thematic Grants