Limmer A, Knolle P A
Center of Molecular Biology, University of Heidelberg, Germany.
Arch Immunol Ther Exp (Warsz). 2001;49 Suppl 1:S7-11.
The induction of peripheral immune tolerance in the liver is a well-known phenomenon that is operative in different situations, such as tolerance to organ transplants and tolerance to oral antigens. The mechanisms leading to peripheral immune tolerance in the liver are still incompletely understood. While different cell populations of the liver have been implicated in and probably contribute in concert to the induction of hepatic immune tolerance, one hepatic cell type in particular seems to be suited for tolerance induction: liver sinusoidal endothelial cell (LSEC). LSEC are microvascular endothelial cells with a unique phenotype reminiscent of dendritic cells and a unique function as antigen-presenting cells for CD4+ T cells. The hepatic microenvironment, i.e. portal venous constituents and soluble mediators from sinusoidal cell populations, tightly control antigen presentation by LSEC to avoid immune-mediated damage. LSEC, in contrast to other endothelial cells, have the capacity to prime naive CD4+ T cells and induce cytokine release. Importantly, naive CD4+ T cells primed by antigen-presenting LSEC differentiate into regulatory T cells, whereas T cells primed by bone marrow-derived professional antigen presenting cells differentiate into Th1 cells. Thus, LSEC represent a new type of organ-resident "non-professional" antigen-presenting cell that appears to be involved in the local control of the immune response and the induction of immune tolerance in the liver.
肝脏中诱导外周免疫耐受是一种众所周知的现象，在不同情况下发挥作用，比如对器官移植的耐受和对口服抗原的耐受。导致肝脏外周免疫耐受的机制仍未完全明了。虽然肝脏的不同细胞群体都与肝脏免疫耐受的诱导有关，并且可能共同发挥作用，但有一种肝细胞类型似乎特别适合诱导耐受：肝窦内皮细胞（LSEC）。LSEC是微血管内皮细胞，具有类似于树突状细胞的独特表型，并且作为CD4+T细胞的抗原呈递细胞具有独特功能。肝脏微环境，即门静脉成分和来自窦状细胞群体的可溶性介质，严格控制LSEC的抗原呈递，以避免免疫介导的损伤。与其他内皮细胞不同，LSEC有能力激活初始CD4+T细胞并诱导细胞因子释放。重要的是，由呈递抗原的LSEC激活的初始CD4+T细胞分化为调节性T细胞，而由骨髓来源的专业抗原呈递细胞激活的T细胞分化为Th1细胞。因此，LSEC代表了一种新型的驻留器官的“非专业”抗原呈递细胞，似乎参与了肝脏免疫反应的局部控制和免疫耐受的诱导。
