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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
- 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.
- Subjects :
- Blood Platelets
0301 basic medicine
Time Factors
T cell
CD8-Positive T-Lymphocytes
030204 cardiovascular system & hematology
Biology
T-Lymphocytes, Regulatory
Transforming Growth Factor beta1
Interferon-gamma
03 medical and health sciences
Interleukin 21
0302 clinical medicine
Cell-Derived Microparticles
Paracrine Communication
Immune Tolerance
medicine
Humans
Cytotoxic T cell
IL-2 receptor
Antigen-presenting cell
Cells, Cultured
Cell Proliferation
Interleukin-6
Tumor Necrosis Factor-alpha
ZAP70
fungi
Interleukin-2 Receptor alpha Subunit
Peripheral tolerance
Cell Differentiation
Forkhead Transcription Factors
Hematology
Natural killer T cell
Molecular biology
Coculture Techniques
Cell biology
030104 developmental biology
medicine.anatomical_structure
Signal Transduction
Subjects
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