课题首次提出TIGIT+Tfr控制Tfh诱导B细胞活化产生特异性抗体介导免疫反应，在参与移植后慢性排斥风险中扮演核心角色。Tfr细胞通过CD155-TIGIT-CD226信号通路，与Tfh竞争性结合FDC和B细胞，抑制Tfh-B细胞间相互作用；促进调节性细胞因子Granzyme-B、TGF-β、IL-10分泌，抑制Tfh细胞功能，介导移植物长期耐受。深入研究Tfr如何通过CD155-TIGIT-CD226信号通路抑制Tfh的功能，寻找Tfr参与调节Tfh体液免疫反应的特异性作用靶点，抑制Tfh-B反应，防止供者特异性抗体产生，促进移植免疫耐受的维持，验证TIGIT/CD226分子是调节GC中Tfh/Tfr细胞平衡的重要靶点，评估血清TIGIT、CD226分子、外周Tfh/Tfr细胞比值作为预测移植物排斥、移植肾失功的生物学标志物在维持移植受者免疫耐受中的作用是本课题的重要研究目标。

The project first proposed that TIGIT+Tfr cells control Tfh-induced B cells activation and antibody-mediated immune response, play a major role in chronic allograft tolerance. Tfr cells interact with FDC and B cells via CD155-TIGIT-CD226 signaling pathway, complete with Tfh cells, inhibit Tfh-B cell interaction; Tfr cells promote the secretion of regulatory cytokine granzyme-B, TGF-β and IL-10, inhibit Tfh cell function and mediate long-term allograft tolerance. Through this project on Tfr-cell regulatory mechanism, we aim to demonstrate Tfr inhibit Tfh through CD155-TIGIT-CD226 signaling pathway, find specific transcription factor within Tfr cells involved in the regulation of Tfh cells and humoral immune response, to inhibit Tfh-B reaction, prevent donor-specific antibody production and promote the maintenance of transplant immune tolerance. We aim to verify that TIGIT/CD226 are important molecules participating in the regulation of Tfh/Tfr cell balance in GC, and evaluate serum TIGIT/CD226 and the ratio Tfh/Tfr cells as predictive biomarkers in allograft rejection and kidney transplant dysfunction.