TCR Activation of Human T Cells Induces the Production of Exosomes Bearing the TCR/CD3/ζ Complex
Abstract
We show in this study that human T cells purified from peripheral blood, T cell clones, and Jurkat T cells release microvesicles in the culture medium. These microvesicles have a diameter of 50–100 nm, are delimited by a lipidic bilayer membrane, and bear TCR β, CD3ε, and ζ. This microvesicle production is regulated because it is highly increased upon TCR activation, whereas another mitogenic signal, such as PMA and ionomycin, does not induce any release. T cell-derived microvesicles also contain the tetraspan protein CD63, suggesting that they originate from endocytic compartments. They contain adhesion molecules such as CD2 and LFA-1, MHC class I and class II, and the chemokine receptor CXCR4. These transmembrane proteins are selectively sorted in microvesicles because CD28 and CD45, which are highly expressed at the plasma membrane, are not found. The presence of phosphorylated ζ in these microvesicles suggests that the CD3/TCR found in the microvesicles come from the pool of complexes that have been activated. Proteins of the transduction machinery, tyrosine kinases of the Src family, and c-Cbl are also observed in the T cell-derived microvesicles. Our data demonstrate that T lymphocytes produce, upon TCR triggering, vesicles whose morphology and phenotype are reminiscent of vesicles of endocytic origin produced by many cell types and called exosomes. Although the exact content of T cell-derived exosomes remains to be determined, we suggest that the presence of TCR/CD3 at their surface makes them powerful vehicles to specifically deliver signals to cells bearing the right combination of peptide/MHC complexes.
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Extracellular vesicles are secreted by both normal and cancerous cells as a means of cell-to-cell communication.
“These vesicles are secreted by both normal cells and cancerous cells as means of cell-to-cell communication [2-5].”
From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [3]
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- Authors
- Blanchard, N., Lankar, D., Faure, F., Regnault, A., Dumont, C., Raposo, G., & Hivroz, C.
- Affiliations
- Inserm (FR)
- Institut National de la Santé et de la Recherche Médicale, Unité 462, Institut d’Hématologie, Hôpital Saint Louis , Paris ,
- Institut National de la Santé et de la Recherche Médicale, Unité 520, and Unité Mixte de Recherche 144, Institut Curie , Paris ,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-04-01
- Volume
- 168
- Issue
- 7
- Pages
- 3235-3241
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1494035906
- Cited by
- 660
- References
- 3
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 25 · 2023: 33 · 2022: 30 · 2021: 53 · 2020: 46 · 2019: 43 · 2018: 45 · 2017: 39 · 2016: 41 · 2015: 27 · 2014: 32 · 2013: 27 · 2012: 23
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- exosomes, TCR/CD3 complex, T cell activation, CD3ε, CD63, protein sorting, CD28, CD45, CXCR4, MHC class I and II, Src family kinases, c-Cbl
- MeSH terms
- Cell-Free System, Clone Cells, Exocytosis, Humans, Kinetics, Lymphocyte Activation, Membrane Proteins, Receptors, Antigen, T-Cell, T-Lymphocytes, Tumor Cells, Cultured, Blotting, Western, Biomarkers, Microscopy, Immunoelectron, Apoptosis, CD3 Complex, Receptor-CD3 Complex, Antigen, T-Cell, Jurkat Cells, Protein Transport, Transport Vesicles
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