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首页> 外文期刊>Transplant immunology >Differential cyclosporin-A sensitivity on survival and activation of umbilical cord and adult peripheral blood CD4+ T cells.
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Differential cyclosporin-A sensitivity on survival and activation of umbilical cord and adult peripheral blood CD4+ T cells.

机译：差异环孢菌素A对脐带和成人外周血CD4 + T细胞存活和激活的敏感性。

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摘要

Enhanced cyclosporine-A (CsA) sensitivity of umbilical cord blood (CB) CD4(+) T cells may contribute to the lower incidence of graft-versus-host disease (GVHD) after mismatched CB transplantation. Interleukin (IL)-15, an IL-2 like gamma-chain signaling cytokine, may bypass CsA inhibition and play an important role in GVHD pathogenesis. The present study examines CsA sensitivity of IL-15-driven CB CD4(+) T cell survival, activation and proliferation, comparing adult peripheral blood (APB) CD4(+) T cell responses. We establish that (1) resting CB CD4(+) T cells were more susceptible to CsA-induced cell death than their adult counterpart; (2) IL-15 help support the survival of resting CB CD4(+) T cell under the influence of CsA, though to a lesser degree that observed in adults; (3) higher CsA sensitivity of CD25 up-regulation following TCR activation was observed in CB but more readily counteracted by IL-15 compared to adults; (4) IL-15-driven proliferation of TCR-activated CD4(+) T cells was more susceptible to CsA inhibition than corresponding adults; and (5) TCR-activated CB CD4(+) T cells surviving high dose CsA (5 microg/ml) in IL-15-supplemented cultures expressed significantly lower percentages of CD45RO(-)/CD25(+) subsets compared to corresponding APB. Taken together, the differential CsA sensitivity and IL-15 response between CB and APB CD4(+) T cells may contribute to the lessened GVHD severity in the setting of CB transplantation.
机译：脐带血（CB）CD4（+）T细胞对环孢素A（CsA）的敏感性增强可能会导致不匹配的CB移植后移植物抗宿主病（GVHD）的发生率降低。白细胞介素（IL）-15是一种类似于γ链信号传导细胞因子的IL-2，可能绕过CsA抑制并在GVHD发病机理中发挥重要作用。本研究检查了IL-15驱动的CB CD4（+）T细胞存活，激活和增殖的CsA敏感性，比较了成人外周血（APB）CD4（+）T细胞的应答。我们确定（1）静息的CB CD4（+）T细胞比成年的同伴更易受CsA诱导的细胞死亡; （2）IL-15有助于在CsA的影响下支持静息CB CD4（+）T细胞的存活，尽管程度要比成年人低。 （3）在CB中观察到TCR激活后CD25上调对CD25上调具有更高的CsA敏感性，但与成人相比，IL-15更容易抵消。 （4）IL-15驱动的TCR激活的CD4（+）T细胞增殖比相应的成年人更容易受到CsA抑制; （5）在补充IL-15的培养物中，高剂量CsA（5 microg / ml）存活的TCR活化CB CD4（+）T细胞表达的CD45RO（-）/ CD25（+）亚群的百分比明显低于相应的APB 。综上所述，CB和APB CD4（+）T细胞之间的差异性CsA敏感性和IL-15反应可能有助于降低CB移植的GVHD严重程度。

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