CTLA4Ig抑制BMP2基因转染的MSCs诱导的免疫应答

目的通过腺病毒介导人细胞毒T淋巴细胞相关抗原4免疫球蛋白(CTLA4Ig)及人骨形态发生蛋白2(BMP2)在骨髓间充质干细胞(MSCs)中的表达,探讨CTLA4Ig对BMP2转染的异基因MSCs诱导的免疫应答的抑制作用。方法以CTLA4Ig和BMP2重组腺病毒转染MSCs。ELISA法检测包装的病毒感染MSCs后,CTLA4Ig及BMP2蛋白的表达;观察CTLA4Ig对混合淋巴细胞反应(MLR)的抑制作用。结果腺病毒载体介导CTLA4Ig和BMP2体外感染的MSCs能够分泌CTLA4Ig及BMP2蛋白,且CTLA4Ig融合蛋白可以有效抑制AdBMP2基因转染的MSCs的刺激作用。结论给予CTLA4Ig腺病毒进行基因治疗可有效的抑制AdBMP2转染的异基因MSCs引起的免疫应答,诱导MSCs移植耐受;为BMP2基因修饰的同种异体间的MSCs移植提供了实验依据。

CTLA4Ig depresses immune response of exogenous BMP2 transgenic MSC transplantation

Objective To investigate the transgene expression of mesencgymal stem cells(MSCs), which was genetically modified by adenovirus to express cytotoxic T lymphcyte-associated antigen 4 immunogloblin(CTLA4-Ig) and bone morphogenetic protein 2(BMP2), and study the immunosuppressive function of CTLA4Ig on Adv-BMP2 gene transduced MSCs allograft. Methods The culture MSCs were transfected by recombinant adenovirus encoding CTLA4Ig and BMP2. The expression of transgene was detected by ELISA, and the CTLA4Ig's inhibition of lymphocyte response was evaluated through mixed lymphocyte reaction (MLR). Results ELISA results showed that MSCs expressed CTLA4Ig and BMP2 protein, and results of MLR demonstrated that CTLA4Ig fusion protein was capable of inhibiting allogeneic MLR. Conclusion CTLA4Ig fusion protein is an effective immunosuppressive immunomodulator, thus worthy of being further investigated its potentials in the induction of MSCs transplantation tolerance.