腺病毒载体介导的CTLA4-Ig基因转移促进异基因小鼠皮肤移植耐受

目的　探讨CTLA4 Ig重组腺病毒 (AdCTLA4 Ig)促进“脾细胞 (spleencells ,SP) 环磷酰胺 (cyclophosphamide ,CP)”系统诱导移植耐受的作用及其机制。方法　BALB c(H 2 d)小鼠经尾静脉注射C57BL 6(H 2 b,B6)小鼠脾细胞和AdCTLA4 Ig颗粒 ,48h后腹腔注射环磷酰胺 ,并同天进行皮肤移植 ,于耐受 2 5d时对受体小鼠进行混合淋巴细胞反应 (mixedlymphocytereaction ,MLR)、迟发型超敏反应 (delayedtypehypersensitivity ,DTH)等耐受状态的检查。结果　B6小鼠的皮肤移植物在耐受的BALB c小鼠中存活期特异延长。MLR和DTH检验证明BALB c小鼠对B6小鼠的脾细胞产生特异性耐受 ,对无关第三者ICR小鼠的脾细胞仍表现出强烈免疫应答。结论　AdCTLA4 Ig颗粒可以明显促进“细胞 环磷酰胺”诱导的异基因皮肤移植耐受 ;克隆排除和克隆无能是耐受诱导的主要因素

AdCTLA4-Ig improves induction of transplantation tolerance to the allogeneic skin allograft in mice

Objective To study the effect and mechanism of A dCTLA4-Ig on tolerance induction based on the "cells-followed-by-CP" syste m. Methods BLAB/c mice (H-2 d) received an injection of allogenic spleen cells from C57BL/6 (B6) mice (H-2 b) and AdCTLA4-Ig via the tail vein, followed by an intraperioneal injection of cyclophosphamide (CP) 48 hours later and then grafted with allogenic skin from B6 mice. Twenty-five days after induction of tolerance the MLR and DTH of tolerance BALB/c mice were exam ined to confirm the tolerance status. Results The surviva l of allogenic skin allografts in the tolerant BALB/c mice was significantly pro longed. The results of MLR and DTH indicated that BALB/c mice were tolerant to t he spleen cells of B6, but not that of ICR mice. Conclusion AdCTLA4-Ig is able to improve the tolerance of allogenic skin graft based by "cells-followed-by-CP" system. Clonal deletion and clone anergy are main m echanisms of the tolerance, while the activity of suppressor cells was not found .