体外诱导免疫抑制功能性CD11b+Gr1+髓样抑制细胞系建立及其对小鼠高危角膜移植排斥反应的调控研究

角膜移植中植床的新生血管及淋巴管化形成高危移植状态，引起极高排斥率。诱导免疫耐受形成是降低高危角膜移植排斥率的关键。CD11b+Gr1+髓样抑制细胞(MDSC)是具有广泛免疫抑制功能的骨髓来源幼稚细胞群。本课题组前期研究证实，正常小鼠的骨髓MDSC细胞无免疫抑制功能，而脓毒血症及荷瘤模型等病理环境下体内诱导的MDSC细胞对引发植片排斥的效应T细胞具有显著抑制作用，过继转移体内诱导MDSC细胞能有效延长移植物存活时间。但是体内诱导MDSC过程代价高昂，安全性低，细胞供体死亡率高。已有报道MDSC具有体外诱导可能，但其亚群作用机制及在诱导角膜移植免疫耐受方面尚无报道。本研究希望建立稳定的具有免疫抑制功能的MDSC体外诱导体系，通过小鼠高危角膜移植动物模型，观察体外诱导的免疫抑制功能性MDSC在角膜移植免疫耐受中的作用，进一步探讨作用机制及途径，为其在角膜移植免疫排斥反应防治中的应用提供依据。

Lymphangiogenesis and angiogenesis after keratoplasty could abolish immune privilege, and subsequently cause the high-risk status and graft rejection. CD11b+Gr1+ myeloid-derived suppressor cells (MDSC) have been used as important negative regulators for an adaptive immune system which generated from bone marrow. Our previous study confirmed that CD11b+Gr1+ cells from naïve mice has no immunosuppressive function, while MDSC from sepsis and tumor-bearing mice significantly inhibited T cell proliferation, and prolonged corneal allograft survival in vivo. However, in vivo induced immuno-suppressive MDSC is not cost-effective, and low safely with high cell donor mortality. Previous report indicated that it is possible to induced MDSC in vitro, but the mechanism of that subsets and the function in corneal transplantation are still unknown. The study hope to establish a steady functionally suppressive MDSC cell line in vitro, observe the effect of adoptive transferring in vitro induced MDSC in mice high-risk corneal transplantation, and to investigate the underlying mechanism and pathway.