Advanced search
Start date
Betweenand
Related content
(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

Full text
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