异基因造血干细胞移植（allo-HSCT）是根治恶性血液病的手段，亲缘间HLA半相合造血干细胞移植（haplo-HSCT）解决了供者缺乏难题，但移植物抗宿主病（GVHD）仍是阻碍allo-HSCT在临床上的广泛开展。我们以往研究发现在小鼠MHC全不相合的GVHD模型上，CD3单抗为基础的预处理方案实现了GVHD和移植物抗白血病效应（GVL）的分离。本项目拟在以往研究基础上建立小鼠半相合GVHD模型，研究CD3单抗预处理方案减轻或预防GVHD并保留GVL效应的机制，特别是深入研究CD3单抗是否通过调控宿主树突状细胞（DC）、巨噬细胞和GVHD靶器官组织保护分子（B7-H1、IDO）的分布和功能，进而影响供者T细胞表达趋化因子受体和归巢分子，从而减少供者T细胞迁移进入GVHD靶器官组织，达到减轻甚或预防GVHD的目的。为本项目的CD3单抗预处理方案顺利转化应用于临床提供临床前期实验依据。

Allogeneic hematopoietic cell transplantation (allo-HSCT) is a curative therapy for hematological malignancies and potentially other cancers..HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an important choice of allo-HSCT and an alternative for the lack of HLA-matched donor ..However, Graft versus host disease (GVHD) still prevents its widely use in clinic.We have reported that in a mouse MHC-mismatched GVHD model, anti-CD3 antibody pretreatment can separate GVL from the GVHD.In this study, based on the preliminary data, we set up haplo-HCT mouse model and study the mechanism by which anti-CD3 prevents GVHD and maintain GVL. We will test the hypothesis that anti-CD3 pretreatment modulates host Dendritic Cells /Macrophages and donor T-cell migration. Also, we will test whether anti-CD3 pretreatment upregulates host tissue expression of B7H1 and IDO to prevent GVHD.By this study, we will have the pre-clinical data for anti-CD3 pretreatment in HSCT. And this study could be important for translational medical use of this novel conditioning regimen.