混合皮肤移植中IL-10在自体角朊细胞诱导局部免疫耐受中的作用

目的：探讨IL-10在混合皮肤移植中角朊细胞诱导的局部免疫耐受中的作用。方法：利用已经建立的MEIC体外模拟系统，检测在引入和未引入自体角朊细胞的实验系统上清中IL-2、IL-4、IL-10和IFN-γ的浓度，并用IL-10基因敲除小鼠实验观察IL-10在诱导抑制中的作用。结果：在未引入自体角朊细胞的MELC体系中，表现的是典型的Th1相关的细胞因子动力学曲线，在加入自体角朊细胞后，则出现了细胞因子由Th1和Th2转换的动力学曲线，且IL-10起着关键的作用，在以IL-10基因knockout小鼠的角朊细胞去替代实验体系中的正常小鼠角朊细胞时，对自体淋巴细胞的同种异体增殖反应的抑制率虽有所下降，但无显著差异，而以IL-10基因knockout小鼠的淋巴细胞替代实验体系中的正常小鼠的淋巴细胞时，对自体淋巴细胞的同种异体增殖反应的抑制作用被显著缓解，表明对抑制起关键调节作用的是自体淋巴细胞来源的IL-10，而非自体角朊细胞分泌的IL-10。结论：在混合皮肤移植中，自体角朊细胞是通过激活Th2细胞，后者分泌大量的IL-10和IL-4等细胞因子来抑制Th1细胞增殖，从而抑制Th1亚群所介导的细胞免疫及移植物排斥来诱导局部免疫耐受的。

The effects of IL-10 in local immuno-suppression induced by auto-keratinocytes in the intermingled skin grafting

Objective:To explore the effects of IL-10 in local immuno-suppression induced by auto-keratinocytes(auto-Kc) in the intermingled skin grafting.Methods:Mixed culture of lymphocytes with epidermal cells of autologous and allogeneic origin were performed with a comparing of cell activity from cytokine-knockout mice.And the Th1/Th2 related cytokine profiles were examined.Results:When allo-Kc were added into the system as control,the Th1-related cytokines were dominantly expressed,but when auto-Kc were added,the system.Expressd a changed cytokine profile,where the Th1-related cytokines were shifted to the Th2 related cytokines.And when a special MELC system was established using cells from BALB/c mice as responders or modulators,auto-Kc's ability of innducing suppression could be partially dimished only when modulator Ka was replaced by its counterpart from IL-10 gene-knockout BALB/c mice in the combinatio La+Eb+Ka~IL-10-/- ,but a relevant replacement of lymphocytes La by La~IL-10-/- led to a more pronounced diminution of suppression,these suggest that Ka-induced suppression depends on IL-10 production mainly by the responding T cells and not by the keratinocytes themselves.Conclusion:Above results indicated that the auto-Kc activated the Th2 cells by indirect recognition pathway,and then the Th2 cells secreted cytokines such as IL-10 and IL-4 which in turn inhibited the proliferation of the Th1 cells,leading to a local immuno-suppression for allo-rejection in the intermingled skin grafting.