TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex.
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 beta, CD3epsilon, and zeta. 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 zeta 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.
Blanchard
Nicolas
N
Institut National de la Santé et de la Recherche Médicale, Unité 520, Institut Curie, Paris, France.
Lankar
Danielle
D
Faure
Florence
F
Regnault
Armelle
A
Dumont
Céline
C
Raposo
Graça
G
Hivroz
Claire
C
D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D017252:CD3 Complex; D002474:Cell-Free System / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D002999:Clone Cells; D005089:Exocytosis / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D021381:Protein Transport / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism* / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D022161:Transport Vesicles / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D017252:CD3 Complex; C115335:CD3E protein, human; D008565:Membrane Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain