在器官移植中应用抗原特异性双阴性T细胞(DN T)是一种很好的特异性治疗策略。我们率先发现转化成熟的DN T细胞主要通过穿孔素途径发挥抗原特异性免疫抑制功能。DN T细胞表达高水平的LAG-3分子和IL-12受体，IL-12显著增高了DN T细胞LAG-3表达并且阻断LAG-3信号下调了DN T的抑制功能，但目前对DN T细胞的抗原特异性获得机制仍不明确。我们拟利用LAG-3基因敲除小鼠，研究LAG-3基因缺失对DN T细胞免疫抑制功能的影响。干预诱导LAG-3表达的IL-12通路，明确树突状细胞通过分泌IL-12促进了DN T细胞高表达LAG-3分子并以trogocytosis作用的方式获得抗原特异性。利用小鼠皮肤移植模型对体内环境中IL-12分泌与LAG-3表达对DN T功能的影响进行深入研究，为未来免疫移植耐受治疗提供帮助。

Regulatory T cell plays a crucial role in transplantation tolerance, and double negative T cell (DN T) is a kind of regulatory cell which provide antigen specific immune suppressive function in transplantation therapy. Our previous studies show that DN T cells express high levels of LAG-3 and IL-12 receptor. IL-12 induced high levels of LAG-3. LAG-3 blocking reduced DN T cell suppressive function. However, the antigen specificity mechanism remains unclear. We intent to study the impact of LAG-3 to DN T cell immune suppressive function with Lag3KO mice. We will first, identify the IL-12 pathway to induction of DN T cell LAG-3 expression; then, figure out the impact of LAG-3 to DN T cell function; finally, discover the trogocytosis phenomenon between LAG-3 and MHC-II. The study findings will help to provide new ideas for transplantation immune therapy.