CTLA-4Ig与ICAM-1单抗促进供者来源的未成熟树突状细胞诱导移植受体免疫耐受  

CTLA-4Ig combined with ICAM-1 mAb promotes immune tolerance induced by donorderived immature dendritic cells in recipient mice

作　　者：丁国善[1] 王全兴[1] 张明[1] 刘玉杉[1] 韩澍[1] 傅志仁[1] 

机构地区：[1]第二军医大学长征医院器官移植中心,上海200003

出　　处：《第二军医大学学报》2006年第3期253-257,共5页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(39870809)~~

摘　　要：目的:研究细胞毒性T淋巴细胞相关抗原4融合蛋白(CTLA-4 Ig)和细胞间黏附分子1(ICAM-1)单抗体内注射促进供者未成熟树突状细胞(imDC)诱导受者免疫耐受的可能机制。方法:实验分对照组(仅输注imDC)、CTLA-4 Ig组、ICAM-1单抗组和CTLA-4 Ig+ICAM-1单抗联合组,每组均以2×106C57BL/6供者imDC经尾静脉输注受鼠(雄性),自imDC输注之日起连续2周向受鼠腹腔内注射CTLA-4 Ig或(和)ICAM-1单抗(0.1 mg/d),DC输注1周后4组均行异位心脏移植,于心脏移植后7 d和21 d,进行免疫学分析。结果:CTLA-4 Ig或联合ICAM-1单抗治疗后均明显抑制同种imDC免疫的移植受体脾脏T细胞对同种抗原刺激的增殖反应,降低淋巴细胞毒活性,明显抑制血清和MLR反应中Th1细胞因子IL-2、IFN-γ的产生,显著提高Th2细胞因子IL-10的水平;明显降低心脏移植受体同种抗体IgG的产生。ICAM-1单抗治疗组的受体T细胞对同种抗原刺激的增殖反应虽有减弱,但与对照组相比没有显著的差异;对MLR反应上清和血清中IL-2的产生有明显的抑制,而对其他细胞因子的产生没有明显的作用。结论:CTLA-4 Ig联合ICAM-1单抗治疗可通过诱导受体T细胞对同种抗原特异性的低反应性,抑制淋巴细胞毒活性和B细胞的体液免疫反应,并促进Th2细胞的极化来促进imDC诱导的同种抗原特异性的免疫耐受。Objective：To investigate the mechanism of CTIL-4Ig combined with Anti-ICAM-1 mAb in promoting immune tolerance induced by donor-derived immature dendritic cells（imDC） in recipient mice. Methods： Male mice were divided into 4 groups： control group （receiving only imDC）, CTLA-4Ig group, ICAM-1 mAb group and CTLA-4Ig＋ICAM-1 group. Mice were transfused with donor-derived imDC 7 days before they received heart transplantation in company with daily injection of ICAM-1 mAb, CTLA-4Ig or both for the following 2 weeks. Immunological analysis was performed in mice 7 days and 21 days after heart transplantation. Results： CTLA 4Ig alone or in combination with ICAM-1 mAb significantly inhibited T cells prolif- eration to alloantigen stimulation, impaired lymphocyte cytotoxicity, suppressed production of IL-2, IFN-7 by Thl, increased production of IL-10, and obviously decreased the production of alloantibody IgG in recipient mice treated with donor-derived imDC. ICAM-1 mAb alone had no significant effects on T cells proliferation and production of Th-derived cytokines except for IL- 2. Conclusion： ICAM-1 mAb combined with CTLA-4Ig can enhance immune tolerance induced by donor-derived imDC in recipient mice through induction of T cells hypo responsiveness, inhibition of lymphocyte cytotoxicity and B cell immunoreation, and promotion of Th2 polarization in vivo.

关 键 词：细胞毒性T淋巴细胞相关抗原4融合蛋白 细胞间黏附分子1 抗体 单克隆 树突状细胞 移植耐受 

分 类 号：R392.4[医药卫生—免疫学]