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NK cell subsets in idiopathic recurrent miscarriage and renal transplant patients.
Journal of Reproductive Immunology ( IF 2.9 ) Pub Date : 2020-02-01 , DOI: 10.1016/j.jri.2020.103098
Bettina Toth 1 , Li Zhu 2 , Hristos Karakizlis 3 , Rolf Weimer 3 , Christian Morath 4 , Gerhard Opelz 5 , Ruben-Jeremias Kuon 6 , Volker Daniel 5
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The present review article compares NK cell subsets and cytokine patterns determined in the peripheral blood as well as results of functional in-vitro assays using peripheral NK cells of idiopathic recurrent miscarriage (iRM) patients with corresponding results obtained in female healthy controls and female renal transplant recipients with good long-term graft function. Immune mechanisms, inducing transplant rejection in long-term transplant recipients might also be able to induce rejection of semi-allogeneic fetal cells in patients with iRM. Consequently, the immune status of transplant recipients with good stable long-term graft function should be different from the immune status of iRM patients. iRM patients show a strong persistent cytotoxic NK cell response in the periphery. Simultaneously, immunostimulatory Th1 as well as immunosuppressive Th2 type lymphocytes in the blood are strongly activated but plasma levels of immunosuppressive Th2 type cytokines are abnormally low. In-vitro, unstimulated NK cell cultures of iRM patients show a strong spontaneous TGF-ß1 release in the supernatant but lower TGF-ß1 levels after stimulation with tumor cell line K562, suggesting strong consumption of TGF-ß1 by pre-activated NK cells of iRM patients that might contribute to the low systemic Th2 type plasma levels. iRM patients do not show a systemic switch to a Th2 type cytokine pattern and one might hypothesize that low TGF-ß plasma levels indicate low TGF-ß levels in the micromilieu immediately before fetal rejection. Persistent TGF-ß deficiency implies a persistent unfavorable micromilieu for pregnancy resulting in failing tolerance induction due to lack of TGF-ß, a condition that might contribute to iRM.

中文翻译:

特发性反复流产和肾移植患者的NK细胞亚群。

本综述文章比较了特发性反复流产(iRM)患者外周血NK细胞在外周血中确定的NK细胞亚群和细胞因子模式以及功能性体外测定的结果,以及在女性健康对照和女性肾移植中获得的相应结果受者具有良好的长期移植功能。免疫机制,在长期移植受者中诱导移植排斥,也可能能够在iRM患者中诱导半同相胎儿细胞排斥。因此,具有良好稳定的长期移植功能的移植受者的免疫状态应不同于iRM患者的免疫状态。iRM患者在外周表现出强烈的持续性细胞毒性NK细胞反应。同时,血液中的免疫刺激性Th1以及免疫抑制性Th2型淋巴细胞被强烈激活,但免疫抑制性Th2型细胞因子的血浆水平异常低。iRM患者的体外,未刺激的NK细胞培养物显示,在用肿瘤细胞系K562刺激后,上清液中有很强的自发性TGF-ß1释放,但TGF-ß1水平较低,这表明预先激活的NK细胞会大量消耗TGF-ß1。可能导致全身Th2型血浆水平低的iRM患者。iRM患者并未表现出全身性转为Th2型细胞因子模式,并且可能假设低TGF-β血浆水平表明在胎儿排异之前,微环境中的TGF-β水平较低。
更新日期:2020-02-01
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