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首页> 外文期刊>Journal of Cellular Physiology >In vitro activated human T lymphocytes very efficiently attach to allogenic multipotent mesenchymal stromal cells and transmigrate under them.
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In vitro activated human T lymphocytes very efficiently attach to allogenic multipotent mesenchymal stromal cells and transmigrate under them.

机译:体外激活人类T淋巴细胞有效地附着在同种异体的多功能间充质基质细胞和轮回他们。

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The regulatory effect of human multipotent mesenchymal stromal cells (MSC) on allogenic T lymphocytes is extremely powerful and of important clinical relevance, but the mechanisms underlying this process are not fully elucidated. We report here that T lymphocytes activated with a sub-mitogenic stimulus such as phytohemaglutinin alone (PHA), or with mitogenic stimuli such as PHA + interleukin-2 (P-IL2), or immobilized anti-CD3 + anti-CD28 mAb (a3-28), tightly bound allogenic MSC and transmigrated within 4 h under them, where they remained for approximately 60 h. Allogenic MSC induced T cell proliferation in cultures containing sub-mitogenic PHA concentrations, and inhibited the mitogenic effect of P-IL2 or a3-28. Anti-gamma-IFN mAb or L-tryptophan complementation partially restored proliferation in P-IL2 and a3-28 cultures, whereby gamma-IFN-synthesizing CD3+ cells were detectable. MSC-lymphocyte contact hindrance using transwells abrogated proliferation in PHA cultures, restored it integrally in P-IL2 cultures, and partially in a3-28 cultures. These data suggest that MSC-induced T lymphocyte regulation results from the combination of various processes. Allogenic cell-cell contact, as demonstrated by the PHA co-cultures is per se stimulatory, whereas gamma-IFN synthesized by activated T lymphocytes, which activates indolamine 2,3-dioxygenase in MSC, and L-tryptophan depletion, which is induced by this enzyme, are inhibitory. Transmigration is nevertheless pivotal for the establishment of the inhibition by these mediators because it targets lymphocytes under the stroma in small extracellular spaces surrounded by MSC, where L-tryptophan is efficiently destroyed, leading to T lymphocyte proliferation arrest. In conclusion lymphocyte transmigration under allogenic MSC potentiates the inhibitory effect of soluble mediators generated by these cells.
机译:人类多能的监管效果间充质基质细胞(MSC)在同种异体的T淋巴细胞是非常强大的重要的临床意义,但机制底层这一过程还没有完全阐明。我们报告,T淋巴细胞激活的sub-mitogenic刺激等独自phytohemaglutinin (PHA),或促有丝分裂的刺激如PHA +白介素2 (P-IL2),或固定化anti-CD3 + anti-CD28马伯(a3-28),紧密地绑定(同种异体的MSC和在4 h下他们,他们仍然为大约60 h。同种异体的MSC诱导T细胞在文化包含扩散sub-mitogenic PHA浓度和抑制P-IL2或a3-28的促有丝分裂的影响。Anti-gamma-IFN马伯或左旋色氨酸互补部分恢复增殖在P-IL2 a3-28文化,gamma-IFN-synthesizing CD3 +细胞可检测。在PHA使用transwells废除扩散文化,恢复它在P-IL2整体文化,部分a3-28文化中。数据表明,MSC-induced T淋巴细胞监管相结合的结果各种流程。的增长表明PHA培养本身刺激,而gamma-IFN合成激活T淋巴细胞,激活indolamine 2,在MSC 3-dioxygenase,色氨酸损耗,引起的酶抑制。然而关键的建立抑制这些介质,因为它的目标淋巴细胞在基质小细胞外空间包围MSC,色氨酸是有效地摧毁,导致T淋巴细胞增殖被捕。淋巴细胞同种异体的MSC下轮回强化溶性的抑制作用这些细胞所产生的介质。

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