与其它B7共刺激途径相比，T细胞免疫球蛋白粘蛋白3（Tim3）及其配体半乳凝集素-9（Galectin-9）途径具有更广泛、更强大的免疫抑制作用。巨噬细胞通过高表达Galectin-9，不仅对初始T细胞具有强大的抑制作用，而且对已致敏的效应性T细胞的功能也有重要调节作用。其仅诱导Th1细胞聚集和凋亡，而Th2细胞几乎不受影响，提示其在移植免疫耐受的诱导过程中可能具有重要作用。然而，该途径在肝移植免疫耐受中的作用机制尚不清楚。我们前期研究发现，肝脏内特殊巨噬细胞Kupffer细胞在大鼠肝移植免疫耐受的诱导过程中起重要作用，但机制并不完全清楚。本项目以Kupffer细胞为靶细胞，从信号转录和基因调控的角度出发，通过阻断或增强其表达，从而了解该途径通过Kupffer细胞对T细胞增殖和功能的具体影响及可能机制，阐明其对大鼠肝脏移植免疫耐受的调节作用，为利用其诱导肝脏移植免疫耐受作一些探索性研究。

T cell immunoglobulin domain and mucin domain-3 (Tim3) and its legand Galectin-9 have more intensive and powerful inhibitory effect on immune regulation than other co-stimulate factors of B7 famliy. Macrophages with high expression of Galectin-9 have strong inhibitory effect ont only on native T cells, but also on actived effector T cells. It only induces the aggregation and apoptosis of Th1 cells, and almost did not affect Th2 cells. That implys Tim3/Galectin-9 pathway could play an importatant role in the induction of immune tolerance. However, the exactly role of this pathway in the immunoterance induction of liver transplantaton remains unclear. Our previous studies have found that Kupffer cell plays an importatant role in the immunoterance induction of liver transplantation in rats.But the detailed mechanisms are still unclear. In the project, the Kupffer cell is chosen as the target cell, the expression of Tim3/Galectin-9 pathway is blocked and enhanced by shRNA interference to explore its effect on proliferation and function of T cell, to elucidate its role in immunoterance induction of rat liver transplantation and do some exporalory work for using this pathway to induce immune tolerance in liver transplanatation.