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  

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

作　　者：曹颖平[1] 陈卫闽[1] 罗心绮[1] 王梅华[1] 郑泽铣[2] 周光炎[2] 

机构地区：[1]福建医科大学附属协和医院,福州350001 [2]上海第二医科大学上海免疫学研究所,上海200025

出　　处：《中国免疫学杂志》2005年第3期187-189,194,共4页Chinese Journal of Immunology

基　　金：国家自然科学基金(39870776);福建省自然科学基金(C0210012);福建省卫生厅青年基金(2002110)资助项目

摘　　要：目的探讨IL10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MELC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IL2、IL4、IL10和IFNγ的浓度,并用IL10基因敲除小鼠实验观察IL10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IL10起着关键的作用,在以IL10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IL10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IL10,而非自体角朊细胞分泌的IL10。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IL10和IL4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。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. [

关 键 词：混合皮肤移植 TH1/TH2 IL-10 

分 类 号：R392.4[医药卫生—免疫学]