分泌型类纤维蛋白原蛋白2在调节性T细胞中表达诱导移植免疫耐受的作用

发布时间：2019-05-28 17:57

【摘要】：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。
[Abstract]:The application of regulatory T cell (Treg) adoptive input is an important method to induce transplantation immune tolerance, but the main problem of clinical application of Treg is that the cell demand dose is huge and the function is unstable in vivo. Secretory fibronectin 2 (sFGL2), as a new effector molecule, can significantly enhance immunomodulatory effect by its high expression in Treg. SFGL2 can specifically bind to low affinity FcyR receptor and block the nuclear transfer of transcription factor NFkB. Decrease the expression of major histochemical compatible antigen II (MHC- II) and costimulatory molecule CD80 on the surface of antigen presenting cells, and inhibit the proliferation of T lymphocytes at the same time. It also promoted the immunomodulatory response of Th2. The T, B and dendritic cellular immune activities of Fgl2 knockout mice (fgl2~ (- / -) were significantly increased. However, the activity of Treg was damaged. The immunomodulatory function of Treg in fgl2~ (Tg) transgenic mice was significantly enhanced. Immune tolerance can be induced by using fgl2~ (Tg) mice as (MHC- completely mismatched) heart transplantation recipients. Natural FGL2 is a tetramer macromolecular glycoprotein. It is found that the functional FGL2 truncated fragment is highly expressed in Treg, and high efficiency Treg, can be prepared so as to meet the needs of clinical application.
【作者单位】：中国医科大学附属第一医院普通外科教研室器官移植外科;
【基金】：国家自然基金面上项目(81373173) 教育部2013年高等学校博士学科点专项科研基金(20132104120002)
【分类号】：R392.4

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