靶向OX40／OX40L通路对CD4＋CD25＋调节性T细胞诱导移植耐受的影响  

CD4＋ CD25＋ regulatory T cells-induced tolerance of islet transplantation by targeting OX40/ OX40L costimulation pathway

作　　者：陈恕求[1] 许斌[1] 任全[1] 王奕铎[1] 王旭辉[1] 李宪昌[2] 陈明[1] 

机构地区：[1]东南大学医学院东南大学附属中大医院泌尿外科,南京210009 [2]哈佛大学医学院BID医学中心附属移植研究中心

出　　处：《中华实验外科杂志》2012年第9期1791-1793,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81070592）;江苏省自然科学基金资助项目（BK2009275）

摘　　要：目的观察OX40／OX40L共刺激通路在调节性T细胞（Treg）诱导移植耐受中的作用。方法建立小鼠胰岛移植模型，分3组：IgG组、抗-OX40L单抗（RM134L）＋抗-CDl54单抗（MRl）组、联合RMl34L＋MRI及抗-CD25单抗（PC61）组。存活超过150d小鼠切除移植侧肾脏，在对侧行同或不同主要组织相容性复合体（MHC）的2次胰岛移植。观察各组平均存活时间（MST）。检测效应性T细胞（nff）、野生型和CDl54敲除小鼠TregOX40表达。检测同基因小鼠胰岛、胰岛移植不加或加RM134L＋MRl治疗的移植物内Foxp3表达。Treg与Teff加或不加OX40激动剂（OX86）以不同比例共培养，检测1reff增殖抑制情况。结果RMl34L＋MRl组MST为〉150d（n=8），较IgG组（19d，n=5）和联合PC61组（23d，n=4）明显延长（P〈0．05）。同或不同MHC的2次胰岛移植MST分别为〉60d（n=3）和17d（n=3）（P〈0．05）。OX40在Teff不表达，在野生型和CDl54敲除小鼠Treg表达。3组小鼠胰岛移植物内Foxp3相对表达量分别为8、21、123AU（P〈0．05）。Objective To observe the role of OX40/OX40L costimulation pathway in the CD4＋ CD25 ＋ regulatory T （Treg） cells-induced tolerance of islet transplantation. Methods Diabetes mellitus was induced in C57BL/6 mice as recipients, and islets from DBA/2 mice were transplanted into the C57BL/6 mice. The recipients were divided into three groups （n = 8 ） ： treated with IgG as controls, anti- OX40L mAb （RM134L） ＋ anti-CD154 mAb （ MR1 ）, and RM134L ＋ MR1 ＋ anti-CD25 mAb. The mean survival time （MST） of allograft was observed. The expression of OX40 in T effeetor cells, Treg cells of wide type and CD154 knock-out mice was detected. The expression of Foxp3 gene in allograft in the ab- sence and absence of anti-OX40L mAb and anti-CD154 mAb was detected. T effector cells and Treg cells were co-cultured at different ratio, and the cell proliferation was assayed. Results The MST in RM134L ＋ MR1 group was 〉 150 days （n = 8）, significantly longer than in IgG group （ MST ＋ 19 days, n = 5 ） and RM134L ＋ MR1 ＋ anti-CD25 mAb （23 days, n =4） （P 〈0. 05）. Anti-OX40L mAb and anti-CD154 mAb treatment could successfully induce tolerance, and also induce donor specific tolerance, but the tolerance was blocked by anti-CD25 mAb treatment （P 〈 0. 05）. OX40 was expressed on the Treg cells surface, whereas the T effector cells had no OX40 expression. The expression level of Foxp3 gene in the allograft treated with anti-OX40L mAb and anti-CD154 mAb was 123 AU, significantly higher than without treat- ment （21 AU） and syngenic control （8 AU） （P 〈0. 05）. After Treg cells were co-cultured with T effector cells at different ratio （ 1 ： 2 and 1 ： 4 ） , the mean count per minute （CPM） of T effector cells was 63 ×10^3 and 41 ×10^3 respectively （P 〈0. 05） , and after addition of OX40, the CPM was 128 ×10^3 and 135 ×10^3 respectively （ P 〉 0. 05 ）. Conclusion CD4 ＋ CD25 ＋ Treg cells were critical to tolerance induction in mice islet transplant reci

关 键 词：胰岛移植 调节性T细胞 耐受 OX40 

分 类 号：R392.1[医药卫生—免疫学]