Division of Immunology, Infectious Diseases and Transplantation, San Raffaele Scientific Institute, Milano, Italy.
Mol Immunol. 2013 Aug;55(1):94-9. doi: 10.1016/j.molimm.2012.10.032. Epub 2012 Nov 10.
CD8 T cells play a critical role in several pathological conditions affecting the liver, most notably viral hepatitis. Accordingly, understanding the mechanisms that modulate the intrahepatic recruitment of CD8 T cells is of paramount importance. Some of the rules governing the behavior of these cells in the liver have been characterized at the population level, or have been inferred by studying the intrahepatic behavior of other leukocyte subpopulations. In contrast to most microvascular beds where leukocyte adhesion is restricted to the endothelium of post-capillary venules, it is now becoming clear that in the liver leukocytes, including CD8 T cells, can efficiently interact with the endothelium of hepatic capillaries (i.e. the sinusoids). While physical trapping has been proposed to play an important role in leukocyte adhesion to hepatic sinusoids, there is mounting evidence that T cell recruitment to the liver is highly regulated and depends on recruitment signals that are either constitutive or induced by inflammation. We review here several specific adhesive mechanisms that have been shown to regulate CD8 T cell trafficking within the liver, as well as highlight recent data that establish platelets as key cellular regulators of intrahepatic CD8 T cell accumulation.
CD8 T 细胞在影响肝脏的几种病理状况中发挥着关键作用,其中最显著的是病毒性肝炎。因此,了解调节 CD8 T 细胞在肝内募集的机制至关重要。一些调节这些细胞在肝脏中行为的规则已经在群体水平上进行了描述,或者通过研究其他白细胞亚群在肝内的行为来推断。与大多数微血管床不同,白细胞黏附仅限于后微静脉的内皮细胞,现在越来越清楚的是,在肝脏中,包括 CD8 T 细胞在内的白细胞可以与肝毛细血管(即窦状隙)的内皮有效地相互作用。虽然已经提出物理捕获在白细胞黏附到肝窦状隙中起着重要作用,但越来越多的证据表明,T 细胞向肝脏的募集受到高度调节,并且依赖于招募信号,这些信号要么是组成型的,要么是由炎症诱导的。在这里,我们综述了几种已被证明可调节 CD8 T 细胞在肝内迁移的特定黏附机制,并强调了最近的数据,这些数据确立了血小板作为肝内 CD8 T 细胞积聚的关键细胞调节剂。