肝效应CD8 + T细胞动力学的决定因素。

StephenW

J Hepatol. 2016 Jul 13. pii: S0168-8278(16)30335-X. doi: 10.1016/j.jhep.2016.07.011. [Epub ahead of print]
Determinants of hepatic effector CD8+ T cell dynamics.Benechet AP1, Iannacone M2.
Author information

• 1Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
• 2Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy; Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. Electronic address: [email protected].
  

AbstractAntigen-specific effector CD8± T cells play a critical role in controlling hepatic infections, such as the one caused by hepatitis B virus (HBV). We review here recent results where we coupled advanced dynamic imaging with dedicated mouse models of HBV pathogenesis to show that circulating effector CD8± T cells aimed at viral clearance initially arrest in liver sinusoids by preferentially docking onto platelets that have previously adhered to liver sinusoids. Upon detachment from platelets, effector CD8± T cells crawl intrasinusoidally irrespective of bloodstream direction, and probe underlying hepatocytes for the presence of antigen by extending filopodia-like protrusions through the sinusoidal fenestrae. Effector CD8± T cells recognize hepatocellular antigen and perform effector functions (i.e. IFN-γ production and hepatocyte killing) while still in the intravascular space, and only later they extravasate in the parenchyma. Finally, we provide our perspective on how, in the next few years, intravital microscopy might shed new light on yet unresolved issues with particular regard to identifying the determinants of hepatic effector CD8± T cell trafficking, antigen recognition and effector functions during hepatocellular carcinoma and understanding the mechanisms whereby intrahepatic T cell priming induces functionally defective T cell responses. A better understanding of how adaptive immunity mediates pathogen clearance and tumor elimination may lead to improved vaccination and treatment strategies for immunotherapy of infectious diseases and cancer.
Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


PMID:27423427DOI:10.1016/j.jhep.2016.07.011

StephenW

肝脏病学杂志。 2016年13月PII：S0168-8278（16）30335-X。 DOI：10.1016 / j.jhep.2016.07.011。 [打印EPUB提前]
肝效应CD8 + T细胞动力学的决定因素。
Benechet AP1，Iannacone M2。
作者信息

    免疫学，移植和传染病，IRCCS圣拉斐尔科学研究所，20132意大利米兰的1区。
    免疫学，移植和传染病，IRCCS圣拉斐尔科学研究所，20132意大利米兰的2区;伟致敬圣拉斐尔大学，20132米兰，意大利;实验影像中心，IRCCS圣拉斐尔科学研究所，20132意大利米兰。电子地址：[email protected]。

抽象

抗原特异性效应CD8±T细胞在控制肝感染，如一个由乙型肝炎病毒（HBV）的关键作用。在这里，我们检讨，我们加上先进的动态影像乙肝发病的专用小鼠模型表明，针对病毒清除循环效应CD8±T细胞最初是在肝血窦通过优先停靠到先前已坚持肝血窦血小板逮捕的最新结果。当从血小板分离，效应CD8±T细胞抓取intrasinusoidally不论血流方向，并通过所述正弦窗孔延伸丝状伪足状突起探测抗原的存在潜在的肝细胞。效应子CD8±T细胞识别肝癌抗原和同时仍然在血管内空间执行效应子功能（即产生IFN-γ和肝细胞杀伤），只有后，他们中的实质外渗。最后，我们为如何，在未来的几年中，活体显微镜可能与特定的方面尚未解决的问题，新的见解透视肝癌期间识别肝效应CD8±T细胞贩运，抗原识别和效应器功能的决定因素和了解其中肝内T细胞吸诱导功能性缺陷的T细胞反应的机制。更好地了解如何获得性免疫介导的清除病原体和肿瘤消除可能导致传染病和癌症的免疫接种改善和治疗策略。

版权所有©2016年欧洲协会肝病的研究。发布时间由Elsevier B.V.保留所有权利。

结论：
    27423427
DOI：
    10.1016 / j.jhep.2016.07.011