TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ζ complex
TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ζ complex
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DOI：
10.4049/jimmunol.168.7.3235
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发表时间：
2002-04-01
影响因子：
4.4
通讯作者：
Hivroz, C
中科院分区：
文献类型：
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作者：
Blanchard, N;Lankar, D;Hivroz, C
在这项研究中，我们发现从外周血中提纯的人T细胞、T细胞克隆和Jurkat T细胞在培养基中释放微泡。这些微囊的直径为50-100 nm，由脂类双层膜分隔，并带有TCRβ、CD3epsilon和Zeta。这种微泡的产生是受调控的，因为它在TCR激活时高度增加，而另一种有丝分裂信号，如PMA和离子霉素，不会诱导任何释放。T细胞来源的微泡也含有Tetraspan蛋白CD63，表明它们起源于内细胞室。它们含有CD2和LFA-1、MHC I类和II类等黏附分子，以及趋化因子受体CXCR4。这些跨膜蛋白被选择性地分选在微囊中，因为没有发现在质膜上高表达的CD28和CD45。这些微泡中存在的磷酸化Zeta表明，在微泡中发现的CD3/TCR来自被激活的复合体池。在T细胞来源的微泡中也观察到转导机制的蛋白、Src家族的酪氨酸激酶和c-Cbl。我们的数据表明，T淋巴细胞在TCR触发后产生小泡，其形态和表型使人想起许多细胞类型产生的内源性小泡，称为外小体。虽然T细胞来源的外切体的确切含量仍有待确定，但我们认为，TCR/CD3在其表面的存在使它们成为强大的载体，专门向携带正确结合的肽/MHC复合体的细胞传递信号。
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.