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A Human Trypanosome Suppresses CD8+ T Cell Priming by Dendritic Cells through the Induction of Immune Regulatory CD4+ Foxp3+ T Cells.
- Source :
- PLoS Pathogens; 6/22/2016, Vol. 12 Issue 6, p1-23, 23p
- Publication Year :
- 2016
-
Abstract
- Although CD4<superscript>+</superscript> Foxp3<superscript>+</superscript> T cells are largely described in the regulation of CD4<superscript>+</superscript> T cell responses, their role in the suppression of CD8<superscript>+</superscript> T cell priming is much less clear. Because the induction of CD8<superscript>+</superscript> 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<superscript>+</superscript> 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<superscript>+</superscript> Foxp3<superscript>+</superscript> T cells that suppressed the priming of transgenic CD8<superscript>+</superscript> T cells by peptide-loaded BMDC. This newly described suppressive effect on CD8<superscript>+</superscript> T cell priming was independent of IL-10, but partially dependent on CTLA-4 and TGF-β. Accordingly, depletion of Foxp3<superscript>+</superscript> cells in mice infected with T. cruzi enhanced the response of epitope-specific CD8<superscript>+</superscript> T cells. Altogether, our data uncover a mechanism by which T. cruzi suppresses CD8<superscript>+</superscript> T cell responses, an event related to the establishment of chronic infections. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 12
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 116318169
- Full Text :
- https://doi.org/10.1371/journal.ppat.1005698