探索移植免疫调控机制、开发新的免疫干预策略，是器官移植领域研究重点；共刺激分子和调节性T细胞（Treg）作用机制研究具有良好的临床应用前景。CD226分子表达于多种免疫细胞，参与其发育分化、增殖杀伤等功能调控，在肿瘤、自身免疫病、移植排斥等领域获得越来越多的重视。本课题组长期从事CD226结构与功能研究。我们发现，CD226敲除小鼠表现出对多种炎症性疾病的抵抗；CD226抗体可抑制自身免疫性疾病进展，可抑制同种异体移植排斥，延长移植物生存期，其机制与上调IL-10等抑制性细胞因子、促进Treg细胞扩增有关，提示CD226在控制移植物排斥方面具有潜在应用价值。本课题拟深入探讨同种异体移植排斥反应中CD226与移植物耐受的关系，阐明CD226调控Treg细胞分化增殖的分子通路，以及诱导Treg细胞促进免疫耐受的可能机制，为移植排斥反应的基础研究和免疫治疗提供新思路和新靶点。

Transplantation is the treatment of choice for most patients with end-stage solid organ diseases, resulting in dramatic improvement in morbidity and mortality. Clinical tolerance induction to permit minimization or cessation of immunosuppressive drugs is one of the key research goals in solid organ transportation. It has been reported that CD226 control the induction of GVHD after BMT and that although CD226-dependent costimulatory effects on CD8 T cells are redundant. How the CD226 control the expansion and functions of Foxp3+ Treg cell in solid organ transplantation are still unknown. CD226 molecule is an adhesion/costimulatory molecule belonging to the immunoglobulin super-family, expressed in a variety subsets of immune cells. CD226 involved in the development, differentiation, proliferation and function of lymphocytes. In our previous study, we found that the CD226 knockout mice showed resistance to a variety of inflammatory disease; CD226 antibody could suppress autoimmune disease progression, and could suppress allograft rejection, prolonging graft survival. The suppress function of CD226 antibody maybe associate with the production of inhibitory cytokines such as IL-10, and Treg cells proliferation, which hinted that CD226 has potential application value in controlling graft rejection. In this study, we plan to investigate the mechanism of CD226 involved in the transplant immune rejection, clarifying the mechanisms of how CD226 regulating the Tregs functions; and provide new possibility of intervention CD226 signal to induce transplantation tolerance.