ICOS—ICOSL和CD28-B7共刺激信号对大鼠角膜移植排斥反应调控效应的比较  

The comparison of ICOS-ICOSL co-stimulatory signal vs CD28-B7 signal on the modulation of corneal allograft survival

作　　者：宫念樵[1] 王海灏[1] 丁召[1] 明长生[1] 张伟杰[1] 陈知水[1] 陈孝平[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所卫生部/教育部器官移植重点实验室,武汉430030

出　　处：《中华器官移植杂志》2009年第8期456-459,共4页Chinese Journal of Organ Transplantation

基　　金：教育部留学回国人员科研启动基金（教外司留[2007]24号）

摘　　要：目的观察阻断可诱导性共刺激分子及其配体（ICOS-ICOSL）或CD28B7共刺激信号对大鼠角膜移植排斥反应的影响，并比较其差异。方法制备腺病毒载体介导的诱导性共刺激分子融合蛋白（AdICOSIg）和腺病毒介导的细胞毒T淋巴细胞抗原4融合蛋白（AdCTLA4Ig）。以DA大鼠为供者，Lewis大鼠为受者，进行角膜移植：受者分别接受经Adβ-Gal、AdICOSIg和AdCTLA4Ig转染的角膜移植，分别为局部Adβ-Gal组、局部AdICOSIg组和局部AdCTLA4Ig组；受者分别接受未经处理的角膜移植，并于移植前24h腹腔注射Adβ-Gal、移植后48h腹腔注射AdICOSIg或移植前24h腹腔注射AdCTLA4Ig，分别为全身Adβ-Gal组、全身AdICOSIg组和全身AdCTLA4Ig组；以接受未经处理的角膜移植者为空白对照。术后每日于手术显微镜下观察移植角膜的透明度，以判断排斥反应的发生情况。基因转染后7d，检测受者血清ICOSIg和CTLA41g的浓度以及抗腺病毒抗体水平。结果空白对照组移植角膜存活时间为（13．1±0．3）d，局部AdICOSIg组、局部AdCTLA4Ig组和全身AdCTLA4Ig组移植角膜的存活时间长于空白对照组，分别为（14．2±0．8）d（P〈0．05）、（15．8±0．6）d（P〈0．01）和（22．7±4．3）d（P〈0．01），局部AdCTLA4Ig组和全身AdCTLA4Ig组各有1例未发生排斥反应。全身AdCTLA4Ig组受者的血清CTLA4Ig浓度较高，其抗腺病毒载体抗体水平则较低。结论CD28137与ICOS-ICOSL共刺激信号在免疫调节效应上存在差异，阻断CD28B7信号所获得的延长移植角膜存活时间的效果优于阻断ICOS-ICOSL者。Objective To block the co-stimulatory pathway of ICOS-ICOSL or CD28-B7, and observe their different effects on the corneal allograft survival. Methods The particles of adenovirusmediated inducible co-stimulator infusion protein （AdICOSIg） and adenovirus-mediated cytotoxic T lymphocyte antigen 4 infusion protein （AdCTLA4Ig） were prepared. The Lewis rats were served as the corneal transplant recipients of DA rats. The recipients were grafted with the donor cornea receiving Adβ-Gal, AdICOSIg or AdCTLA4Ig gene transfection, and grouped as local Adβ-Gal, local AdICOSIg and local AdCTLA4Ig, respectively. In another series, the recipients were grafted with no treated donor corneas but receiving Adβ-GaL intro-peritoneal injection （ip） 24 h before transplantation, AdlCOSlg ip 48 h after transplantation or AdCTLA4Ig ip 24 h before transplantation,and grouped as sys Adβ-Gal, sys AdICOSIg and sys AdCTLA4Ig respectively. In the empty control group, neither the donors nor the recipients received any treatment. The transparency of the grafts was observed by a surgical microscope daily to define the rejection onset. Seven days after gene transfection, the sera of the recipients were detected for the level of ICOSIg or CTLA4Ig, and the titre of the anti-adenovirus antibody. Results The survival of the empty control group was （13. 1 ± 0. 3） days,and that of local AdlCOSIg,local AdCTLA4Ig and sys AdCTLA4Ig groups was prolonged as （14. 2 ± 0. 8） days （P〈 0. 05）, （ 15.8 ±0. 6） days （P〈0. 01） and （22.7 ± 4. 3） days （P〈0. 01 ）. Both local AdCTLA4Ig and sys AdCTLA4Ig groups had one case without rejection onset. The CTLA4Ig expression in the sera was high in sys AdCTLA4Ig, meanwhile the anti-adenovirus antibody titre was low. Conclusion In the corneal transplant model, the blockade of ICOS-ICOSL signal exhibits a slight effect to modulate rejection in comparison to that of CD28 B7 signal. The blockade of CD28 B7 signal presents a superior prolongation to the ICOS-ICOSI. signal in the

关 键 词：基因疗法 角膜移植 腺病毒科 抗原 CD28 抗原 CD80 

分 类 号：R686[医药卫生—骨科学]