CTLA-4 Ig融合蛋白抗小鼠同种心脏移植排斥的效果及其机制  

Anti-rejection effects of CTLA-4 Ig fusion protein on cardiac allografts in mice and its mechanism in vivo

作　　者：丁国善 王全兴[2] 张明 孙文佶[2] 刘玉杉 陈国友[2] 付志仁 曹雪涛[2] 

机构地区：[1]长征医院普通外科 [2]第二军医大学基础医学部免疫学教研室,上海200433

出　　处：《第二军医大学学报》2001年第6期554-557,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金资助项目 (3 9870 80 9)

摘　　要：目的 :研究细胞毒性 T淋巴细胞相关抗原 4(CTL A - 4,CD15 2 ) Ig融合蛋白 (CTL A- 4Ig)抗小鼠同种心脏移植排斥的效果及其体内作用的机制。 方法 :以 C5 7BL / 6小鼠为供者 ,BAL B/ c小鼠为受者行异位心脏移植术 ,分别腹腔注射 CTL A-4Ig[10 0μg/ d,共 15次 ]、γ-球蛋白对照抗体及 PBS,观察移植供心的存活时间 ;研究腹腔注射 CTL A- 4Ig后受体小鼠 T细胞对同种抗原反应性的变化以及对 T细胞亚群分化的影响。结果 :同种心脏移植的小鼠腹腔注射 CTL A- 4Ig后 ,移植心脏存活时间较对照组显著延长 ,40 %移植心脏的存活时间长达 2个月以上。 CTL A- 4Ig治疗后诱导受体小鼠 T细胞对同种抗原低反应性 ,但对第三者抗原的反应性无影响。受体血清中的 Th1来源的 IL - 2、IFN-γ均明显低于 PBS对照组 ,而 Th2来源的 IL - 10的水平则明显高于对照组 ,IL- 4未见明显的改变。结论 :CTL A- 4Ig治疗后可通过诱导受体小鼠 T细胞对同种抗原低反应性以及受体 T细胞由 Th1向 Th2分化 ,诱导供者特异性免疫耐受的产生 。Objective: To determine the anti rejection effects of CTLA 4 Ig fusion protein on cardiac allografts in mice and to discuss its mechanism in vivo . Methods: BALB/c recipients were performed cervical heterotopic heart transplantation to receive C57BL/6 donor hearts with a cuff technique. BALB/c recipients were intraperitoneally injected with CTLA 4 Ig [100 μg/d×15 times], control immunoglobins and PBS to observe the survival time of allografts with ECG. The hyporesponsiveness of splenic T cell, the polarization of the T subsets were analyzed after the recipients treated with CTLA 4 Ig. Results: After treated with CTLA 4 Ig, the survival of cardiac grafts was significantly prolonged compared with the control groups, and more than 40% cardiac grafts survived over 2 months. The splenic T cells isolated from recipients did not respond to restimulation of donor splenocytes in MLR, but did exhibit the capacity to proliferate in response to C3H splenocytes(third party).The levels of IL 2 and IFN γ decreased and the level of IL 10 increased in CTLA 4 Ig treated mice. Conclusion: Administration of CTLA 4 Ig can induce donor specific tolerance, which induce T subsets to polarize toward Th2 subset and hyporesponsiveness to alloantigen, and prolong the survival time of the cardiac grafts effectively. [

关 键 词：CTLA-4Ig融合蛋白 异位心脏移植 移植物排斥 小鼠 

分 类 号：R654.2[医药卫生—外科学] R392.4[医药卫生—临床医学]