自体角朊细胞引起Th1向Th2极化抑制同种异体免疫应答

Suppression of Alloreactions by Polarizing Th1 to Th2 Subset after Superposition of the Recipient's Keratinocytes into a Mixed Epidermal Cell and Lymphocyte Culture (MELC) System

我们已有的工作揭示 ,在混合皮肤移植的体外模型MELC中 ,自体角朊细胞可通过间接递呈同种异体抗原诱导免疫抑制。本文在此基础上 ,进一步分析其中Th1和Th2相关细胞因子含量的变化。结果发现 :(1)向MELC引入自体角朊细胞后约 32h ,原同种异体应答中出现的IFN γ和IL 2分泌格局开始让位于IL 4和IL 10 ,6 4h后IFN γ和IL 2完全消失 ,表明发生了淋巴细胞Th1向Th2亚群的极化 ;(2 )单抗封闭试验表明 ,IL 10在其中起关键作用 ;(3)经自体和异体角朊细胞调变过的淋巴细胞对MELR的作用相反 ,前者抑制 ,后者促进。这是首次从T亚群相互作用上探索并揭示混合皮肤移植引起局部免疫耐受的机制。

We reported previously that the autologous keratinocytes (auto Kc) could induce immunosuppression through indirect presentation of alloantigens when being superposed as a regulator into primary mixed cell culture(MELC)system,in which auto lymphocytes and allo epidermal cells were adopted as responders and stimulators to mimic allo reaction in the intermingled skin grafting for treatment of severe burn patients In this work the profile changes of Th1 and Th2 related cytokine are examined with the auto Kc and allo Kc superposed MELC system Firstly,the original secretion of IFN γ and IL 2 in the alloreaction was observed to be replaced by IL 4 and IL 10 at 32h after auto Kc was introduced into MELR,and at 64h,the IFN γ and IL 2 were completely undetectable Secondly,the IL 10 was a critical factor for down regulation of the MELR,which was demonstrated by a blocking assay with anti IL 10/IL 4 mAbs Thirdly,a suppressive or helpful activity on MELR were detected for the Kc modulated lymphocytes,which were isolated from recipient's (auto ) and donor's (allo ) keratinocytes superposed MELC,respectively It is believed therefore that the polarization of T subsets from Th1 to Th2 induced by auto Kc,could attribute to the local immune tolerance appeared in the intermingled skin transplantation,in which auto skin islets are mosaiced onto allo skin sheet for grafting