近交系大鼠肝移植自发免疫耐受模型的建立及其CD8^+ CD28^- T细胞的作用  

Establishment of orthotopic liver transplantation model of inbred rats with spontaneous tolerance and study on role of CD8^+ CD28^- T cells

作　　者：刘玉兰[1] 肖文斌[1] 陈国栋[1] 孙君泓[2] 

机构地区：[1]北京大学人民医院消化科北京大学器官移植中心,北京市100044 [2]澳大利亚国家肝移植中心

出　　处：《中华肝胆外科杂志》2005年第7期481-484,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：国家自然科学基金项目资助(NO.30240051)

摘　　要：目的建立近交系大鼠原位肝移植自发免疫耐受模型,并研究CD8+CD28-T细胞在自发免疫耐受形成中的作用。方法双袖套法建立原位肝移植模型;流式细胞技术检测CD8+CD28-T抑制细胞含量变化;利用补体细胞毒和免疫磁珠方法分离CD8+CD28-T细胞,通过体外混合淋巴细胞反应验证其抑制功能。结果我们成功建立了BN(供体)→LEW(受体)原位肝移植自发免疫耐受模型,并发现自发免疫耐受模型大鼠脾脏CD8+CD28-T细胞含量(23.7%±7.2%)显著高于正常大鼠(5.4%±1.5%)和急性排斥组大鼠(6.0%±1.3%),而且,分离纯化后的自发免疫耐受组大鼠脾脏CD8+CD28-T细胞可以抑制混合淋巴细胞反应的增殖,但急性排斥组大鼠脾脏CD8+CD28-T细胞无抑制功能。结论BN(供体)→LEW(受体)原位肝移植模型为自发免疫耐受;脾脏CD8+CD28-T细胞作为一种T抑制细胞,在自发免疫耐受的形成过程中具有重要作用。Objective To establish the orthotopic liver transplantation （OLT） model of inbred rats and explore the role of spleen CD8^＋CD28^-T cells in spontaneous tolerance of the model. Methods The OLT model of inbred rats was established according to double-sheeve technique. The propor tional changes of spleen CD8^＋CD28^-T cells were determined by flow cytometry. Spleen CD8^＋CD28^-T cells were sorted by complement-dependent cytotoxicity and immunomagnetic beads. The suppressing activity of the spleen CD8^＋CD28^- T cells was tested by mixed lymphocyte reaction in vitro. Resuits An OLT model of spontaneous tolerance was established between BN （donor） and LEW （recipient） inbred rats. After OLT, spleen CD8^＋CD28^-T cells in the spontaneous tolerance model were elevated to 23.7% 7.2% , which was more than that in the normal control （5.4% 1.5%） and acute rejection model 6.0% 1.3%）. The spleen CD8^＋CD28^-T cells isolated from the spontaneous tolerance model but not acute rejection model could inhibit the proliferation of mixed lymphocyte reaction. Conclusions The spleen CD8^＋CD28^-T cells isolated from the spontaneous tolerance model are an unique kind of suppressor T cells. Meanwhile, they might play an important role in induction of spontaneous tolerance.

关 键 词：近交系大鼠 肝移植 自发免疫耐受 动物模型 CD8^+CD28^-T细胞 

分 类 号：R657.3[医药卫生—外科学]