GVHD是 allo-HSCT后主要并发症和死亡原因，我们和国外前期研究表明Treg可防治GVHD而不影响GVL。但新近对Treg可塑性的认识、尤其是体外工程化Treg比天然Treg更具有可塑性，这使Treg防治GVHD受到挑战。本研究基于Treg可塑性依赖局部内环境；GVHD是由免疫细胞与炎性/细胞因子参与的病理过程、有组织器官特异性与差异性。利用正常/白血病急性GVHD 小鼠及体外GFP 标记Treg，研究工程化和天然Treg在GVHD各组织器官的可塑性和向Th效应细胞转化的差异性；Treg可塑性对GVHD发生与发展及GVL的影响；Treg可塑性与GVHD靶组织器官的局部内环境包括：炎性/细胞因子、免疫细胞和靶组织细胞表面细胞/趋化因子受体表达的关系等。揭示Treg在各GVHD靶组织可塑性及GVHD效应因子致靶组织器官特异性与差异性机理，为临床GVHD防治提供理论依据。

Graft-versus-host disease (GVHD) is a major complication and cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated that Regulatory T cells(Treg) might be utilized to prevent and treat GVHD without compromising graft-versus-leukemia (GVL). Recently, there have been increasing reports that challenge this view by demonstrating that Treg retain developmental plasticity and engineered Treg in vitro might be more plastic than natural Treg. The plasticity of Treg depends on the local internal environment. GVHD is a complex pathological process involving active immune cells and inflammatory factors/cytokines with tissue specificity and diversity. To explore the plasticity of Treg and its effects on GVHD as well as GVL, acute GVHD model of normal/leukemic mice were constructed and Treg were labelled with green fluorescent protein(GFP).The studies include following:(ⅰ) exploring the plasticity of engineered/natural Treg and the difference of plasticity in various target organs of acute GVHD; (ⅱ) studying the effects of Treg plasticity on the occurrence and development of GVHD as well as GVL; (ⅲ)studying the immune cells, inflammatory factors/cytokines and the expression of cytokine/chemokine receptors in target organs of acute GVHD. These studies will bring to light the mechanisms of the plasticity of Treg and the organ specificity and the effectors diversity of acute GVHD, and supply theoretical basis for Treg in preventing and treating GVHD.