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Complex1
*
Institut National de la Santé et de la Recherche Médicale, Unité 520, and
Unité Mixte de Recherche 144, Institut Curie, Paris, France; and
Institut National de la Santé et de la Recherche Médicale, Unité 462, Institut d’Hématologie, Hôpital Saint Louis, Paris, France
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 
, CD3
, and
. 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 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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