论文部分内容阅读
应用调节性T细胞(Treg)过继输入是诱导移植免疫耐受的一种重要手段,但临床应用Treg的主要问题是细胞需求剂量巨大而且在体内功能不稳定。分泌型类纤维蛋白原蛋白2(sFGL2)做为一种新型效应分子,其在Treg高表达可以显著增强免疫调节作用。sFGL2可以与低亲和力FcyR受体特异性结合,阻断转录因子NFkB的核转移,降低抗原递呈细胞表面主要组织相容性抗原Ⅱ(MHC-Ⅱ)及共刺激分子CD80的表达,同时抑制T淋巴细胞增殖反应,并促进Th2类免疫调节反应。fgl2基因敲除小鼠(fgl2~(-/-)的T、B、树突细胞免疫活性均显著增强,而Treg的活性受损。fgl2转基因小鼠(fgl2~(Tg))的Treg免疫调节功能则明显增强。应用fgl2~(Tg)小鼠作为(MHC-完全非匹配)心脏移植受体可以诱导出免疫耐受。天然FGL2为四聚体大分子糖蛋白,发现有功能的FGL2截短片段并将其高表达于Treg中,可以制备出高效能Treg,从而有希望满足临床应用需求。
Adoptive adoptive transfer of regulatory T cells (Tregs) is an important means of inducing immune tolerance in transplantation. However, the main problem of clinical application of Tregs is that they require large doses of cells and are unstable in vivo. As a novel effector molecule, secreted fibrinogen protein 2 (sFGL2), which is highly expressed in Treg, can significantly enhance the immunomodulatory effect. sFGL2 can specifically bind to low-affinity FcyR receptor, block the nuclear translocation of transcription factor NFkB, reduce the expression of major histocompatibility antigen (MHC-Ⅱ) and costimulatory molecule CD80 on the surface of antigen presenting cells, and inhibit the expression of T Lymphocyte proliferation response, and promote Th2 immune response. The immunological activities of T, B and dendritic cells in fgl2 knockout mice (fgl2 ~ (- / -)) were significantly increased, but the Treg activity was impaired. Treg immunoregulation in fgl2 transgenic mice Function was significantly enhanced.Immune tolerance can be induced by using fgl2 ~ (Tg) mice as (MHC-completely mismatched) heart transplant recipients.Focal FGL2 is a tetrameric macromolecule glycoprotein and a functional FGL2 truncated fragment was found Segment and its high expression in Treg, can produce high-performance Treg, which hope to meet the needs of clinical applications.