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Ectosomes released by platelets induce differentiation of CD4+ T cells into T regulatory cells

Ectosomes released by platelets induce differentiation of CD4+ T cells into T regulatory cells

Authors :
Jürg A. Schifferli
Francesca Amicarella
Salima Sadallah
Giandomenica Iezzi
Ceylan Eken
Source :
Thrombosis and haemostasis, Thromb Haemost.
Publication Year :
2014
Publisher :
Georg Thieme Verlag KG, 2014.

Abstract

SummaryAccumulating evidence suggests an immune-modulatory role for platelets (PLT) and PLT-derived microvesicles. In particular, ectosomes, i.e. vesicles budding from PLT surface, have been shown to exert immunosuppressive activities on phagocytes. Here we investigated the effects mediated by PLT-derived ectosomes (PLT-Ecto) on CD4+ T cells. Exposure of activated CD4+ T cells to PLT-Ecto decreased their release of IFNγ, TNFα and IL-6, and increased the production of TGF-β1. Concomitantly, PLT-Ecto-exposed CD4+ T cells displayed increased frequencies of CD25high Foxp3+ cells. These phenomena were dose-dependent and PLT-Ecto specific, since they were not observed in the presence of polymorphonuclear- and erythrocyte-derived ectosomes. Analysis of specific T cell subsets revealed that PLT-Ecto induced differentiation of naïve T cells into Foxp3+ cells, but had no effect on predifferentiated Foxp3+ regulatory T cells (Tregs). Importantly, PLT-Ectoinduced Foxp3+ cells were as effective as peripheral blood Tregs in suppressing CD8+ T cell proliferation. PLT-Ecto-mediated effects were partly dependent on PLT-derived TGF-β1, as they were to some extent inhibited by PLT-Ecto pretreatment with TGF-β1-neutralising antibodies. Interestingly, ectosome-derived TGF-β1 levels correlated with Foxp3+ T cell frequencies in blood of healthy donors. In conclusion, PLT-Ecto induce differentiation of CD4+ T cells towards functional Tregs. This may represent a mechanism by which PLT-Ecto enhance peripheral tolerance.

Details

ISSN :
2567689X and 03406245
Volume :
112
Database :
OpenAIRE
Journal :
Thrombosis and Haemostasis
Accession number :
edsair.doi.dedup.....7047d3d083a3521e71af66c382b708c5
Full Text :
https://doi.org/10.1160/th14-03-0281