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

Salima Sadallah; Francesca Amicarella; Ceylan Eken; Giandomenica Iezzi; Jürg A. Schifferli

doi:10.1160/th14-03-0281

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 112(06): 1219-1229
DOI: 10.1160/th14-03-0281

Platelets and Blood Cells

Schattauer GmbH

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

Salima Sadallah^*

¹Department of Biomedicine, University Hospital Basel, Switzerland

,

Francesca Amicarella^*

²Institute of Surgical Research and Department of Biomedicine, University Hospital Basel, Switzerland

,

Ceylan Eken

¹Department of Biomedicine, University Hospital Basel, Switzerland

,

Giandomenica Iezzi⁺

²Institute of Surgical Research and Department of Biomedicine, University Hospital Basel, Switzerland

,

Jürg A. Schifferli⁺

¹Department of Biomedicine, University Hospital Basel, Switzerland

› Author Affiliations

Abstract

Summary

Accumulating 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 CD25^high 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.

Keywords

Microparticles - ectosomes - extracellular vesicles - platelet immunology - T cell differentiation

Full Text

References

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