Mechanisms of murine spontaneous liver transplant tolerance.
Liver transplant is associated with the induction of peripheral immune tolerance. Liver allografts are accepted spontaneously in most combinations of mismatch in major histocompatibility complex, without any requirements for immunosuppression. Liver nonparenchymal cells (especially dendritic cells and Kupffer cells), costimulatory pathways, and activated T-cell apoptosis may contribute to the induction of liver tolerance. Therefore, liver tolerance is an active process that includes T-cell activation, proliferation, infiltration of the allograft, and T-cell apoptosis. Liver dendritic cells may modulate the amount of alloreactive T cells in liver graft recipients by expressing the coinhibitory molecule programmed death-ligand 1 and the immunosuppressive enzyme indoleamine 2,3-dioxygenase. Liver dendritic cells also may induce activated T-cell apoptosis and Foxp3+ regulatory T cells. Future studies may clarify the precise function of liver nonparenchymal cells, the interactions between programmed death-ligand 1 and other costimulatory signals, and the contribution of the liver microenvironment to the induction and expansion of Foxp 3 regulatory T cells.
Department of Hepatobiliary-Pancreatic Surgery, The Third Hospital of Jilin University (China-Japan Union Hospital), Changchun, China.
Hongyu
H
Liu
Lianyue
L
Guan
Zhuonan
Z
Li
Zhanpeng
Z
Wang
Wei
W
Li
D064591:Allografts; D000818:Animals; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects; D008213:Lymphocyte Activation; D051379:Mice; D023421:Models, Animal; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D023001:Transplantation Tolerance