CD1d在小鼠皮肤移植排斥反应中的作用及机制研究  

Role and mechanisms of CD1d in skin graft rejection in mice

作　　者：许相范 徐显辉 叶承祖 林艳丽(指导) XU Xiangfan;XU Xianhui;YE Chengzu;LIN Yanli(Department of Pathology,Hospital of the 73rd Group Army of the PLA,Xiamen 361003,China)

机构地区：[1]中国人民解放军陆军第七十三集团军医院病理科,厦门361003 [2]厦门医学院附属第二医院病理科,厦门361021

出　　处：《中国免疫学杂志》2022年第12期1409-1413,1420,共6页Chinese Journal of Immunology

基　　金：福建省自然科学基金青年创新项目(2009D011)。

摘　　要：目的:探讨CD1d在小鼠皮肤移植排斥反应中的免疫调节作用及其机制。方法:利用两种基因缺失小鼠的同种异体皮肤移植实验模型,观察CD1d与移植皮片存活时间的相关性。采用RT-PCR和流式细胞术检测NKT细胞,探讨CD1d的作用机制。以实时荧光定量PCR分析CD1d与受体小鼠体内细胞因子微环境改变的相关性。最后,通过阻断细胞因子、激活NKT细胞和过继免疫法证实结果。结果:CD1d基因缺失时移植物存活时间明显长于野生型(P<0.001),NKT细胞数量较野生型明显减少(P<0.05),而IL-10和TGF-β水平明显增高(P<0.05,P<0.001)。脾淋巴细胞过继免疫、α-GalCer治疗和IL-10阻断均可缩短移植物存活时间。结论:CD1d分子通过以CD1d-NKT细胞为轴的免疫反应,抑制NKT细胞的激活和细胞因子微环境的改变,在器官移植早期排斥反应中起到举足轻重的作用。Objective:To investigate the immunomodulatory effects and mechanisms of CD1d on skin graft rejection in mice.Methods:The relationship between CD1d and graft survival time was observed by using two kinds of allogeneic skin transplantation models in CD1d gene knockout mice.NKT cells were detected by RT-PCR and flow cytometry to explore the mechanism of CD1d.The correlation between CD1d and cytokine milieu of recipient mice was analyzed by real time PCR.Finally,the results were confirmed by blocking cytokines,activating NKT cells and adoptive immunization.Results:The CD1d deficient grafts survival time was significantly longer than wild-type(P<0.001)and the number of NKT cells was decreased significantly compared with wild type(P<0.05),but IL-10 and TGF-βlevels were significantly increased(P<0.05,P<0.001).Adoptive immunity of splenic lymphocytes,α-GalCer therapy and IL-10 blockade could shorten the survival time of grafts.Conclusion:The biological axis of CD1d-NKT cell based immune response plays an important role in the innate immune response in the early stage of organ transplantation through the activation of NKT cells and the changes of cytokine milieu.

关 键 词：CD1D 皮肤移植 IL-10 TGF-β NKT细胞 

分 类 号：R392.4[医药卫生—免疫学]