中文摘要
我们已证明体外诱导正常小鼠幼稚T细胞产生的新型CD8+Foxp3-CD103+iTreg细胞具有显著体内外免疫抑制作用,进一步证明CD103在CD8+iTreg细胞免疫抑制功能中发挥了关键性作用。我们预实验在健康成人、狼疮患者、狼疮小鼠中均诱导产生类似表型及功能的CD8+CD103+iTreg细胞。那么,CD8+CD103+iTreg细胞能否诱导免疫耐受,并对狼疮小鼠具有治疗作用?我们前期研究显示iTreg细胞在体内外能直接抑制狼疮小鼠自身反应性B细胞的反应。据此,我们提出假设:CD8+CD103+iTreg细胞诱导免疫耐受,并通过自体细胞诱导、扩增起治疗作用。本项目拟应用狼疮小鼠模型,采用细胞培养、流式细胞术等方法,旨在证明这一假设并获得自体CD8+CD103+iTreg细胞诱导免疫耐受并对狼疮小鼠具有治疗作用的可靠证据,为探索系统性红斑狼疮及狼疮肾炎新的治疗方法提供科学依据。
英文摘要
We have proved that naive T cells in normal mice in vitro can be induced to produce a novel CD8+regulatory T cell subsets, namely CD8+Foxp3-CD103+iTreg cells, which have significant suppressive activity in vitro and in vivo.Further evidence show that CD103 has played a key role in the immunosuppressive function of these CD8+ iTreg cells. Our preliminary experiments showed that a similar phenotype and function of CD8+CD103+iTreg cells in healthy adult volunteers, lupus patients and lupus mice can be induced.But it is not clear whether CD8+CD103+ iTreg cells can induce immune tolerance and has therapeutic effects in lupus mice. We had demonstrated that iTreg cells directly suppress autoreactive B cells in vitro and in vivo in lupus mice. Thus, we propose that CD8+CD103+iTreg cells may induce immune tolerance, and has therapeutic effects in lupus mice through autologous cell induction and amplification. The project intends to use lupus mice model, adopt cell culture, flow cytometry and other methods, aiming to prove the hypothesis and obtain the reliable evidence that CD8+CD103+ iTreg cells induce immune tolerance and has therapeutic effects in lupus mice. This project will provide scientific evidence for exploring new treatment of systemic lupus erythematosus and lupus nephritis.
