调节性γδT细胞在急性移植物抗宿主病中的作用及机理研究

Treg致自身免疫性疾病使其用于防治GVHD受到挑战。Treg致自身免疫性疾病可能与Treg可塑性相关，而可塑性又与Treg不均一性有关，故进一步细分Treg亚群十分必要。新近发现一种比Treg更均一的细胞-γδTreg，它属于γδT细胞，表达Foxp3和CD25，有免疫抑制功能。有研究认为γδTreg可抑制自身免疫性疾病的发生与发展。我们前期研究发现allo-HSCT患者GVHD发生率与供者γδTreg数量负相关，提示γδTreg可能对GVHD有抑制作用。本研究拟①建立γδTreg体外最佳扩增体系；②在体外、动物模型和allo-HSCT患者中，采用流式、PCR和ELISA等方法，检测外周血和GVHD累及组织器官中各淋巴细胞亚群和相关细胞因子的表达等，探讨γδTreg生物学特性，揭示γδTreg对GVHD、GVL和造血重建的影响及机理，为临床开展γδTreg防治GVHD提供理论依据。

Experimental and clinical studies have demonstrated that regulatory T cells (Treg) could be utilized to prevent and treat graft-versus-host disease (GVHD). However, there have been increasing reports that challenge this view by demonstrating that Treg might lead to autoimmune diseases. Treg inducing autoimmune diseases might be associated with the plasticity of Treg, and the plasticity was related to the heterogeneity of Treg population. Therefore, a further subdivision of Treg population is quite necessary. Lately, investigators found a more homogeneous cell population- regulatory γδ T cells (γδ Treg), which belonged to γδ T cells, expressed Foxp3 and CD25, and had immunosuppressive function. Some studies reported that γδ Treg could inhibit the occurrence and development of autoimmune diseases. Our previous study found that the incidence of GVHD in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) was negatively correlated with the number of γδ Treg subsets in transplant donors, suggesting that γδ Treg might have inhibitory effect to GVHD. In this study, the optimal ex vivo expansion system for γδ Treg would be established. To explore the biological characteristics of γδ Treg，as well as the effects and mechanisms of γδ Treg on GVHD, graft-versus-leukemia (GVL) and hematopoietic reconstitution, the expressions of each lymphocyte subset and related cytokines in peripheral blood and target organs of GVHD would be detected in vitro,animal model and recipients of allo-HSCT, using fluorescence activated cell sorter (FACS), polymerase chain reaction (PCR), enzyme-linked immuno sorbent assay (ELISA) and other methods. These studies will supply theoretical basis for γδ Treg in preventing and treating GVHD.