T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells
T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells
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DOI：
10.1002/hep.21378
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发表时间：
2006-11-01
期刊：
影响因子：
13.5
通讯作者：
Bertolino, Patrick
中科院分区：
文献类型：
--
作者：
Warren, Alessandra;Le Couteur, David G.;Bertolino, Patrick
肝脏具有诱导耐受性的既定能力。最近的证据表明，这种独特的属性可能与其独特的架构，使T细胞被激活原位独立的淋巴组织。与淋巴结活化的T细胞不同，肝活化的T细胞是短暂的，这可能是导致“肝耐受效应”的机制。尽管肝细胞作为致耐受性抗原呈递细胞的潜在作用已被证实，但这些细胞是否能够在生理环境中与CD 8（+）T细胞相互作用的问题仍然存在争议。矛盾的免疫学教条，说明天真的T淋巴细胞被阻止与实质细胞在非淋巴器官内的一个不可穿透的内皮屏障，我们在这里表明，独特的形态的肝窦内皮细胞（I-SEC）允许淋巴细胞和肝细胞之间的相互作用。使用电子显微镜，我们证明了肝脏驻留淋巴细胞以及循环的幼稚CD 8（+）T细胞通过细胞质延伸穿透包围LSEC的内皮开窗与肝细胞直接接触。此外，初级T细胞活化所需的分子，MHC I类和ICAM-1的表达在肝细胞上极化至窦周细胞膜，从而最大化与循环淋巴细胞相互作用的机会。总之，这项研究已经确定，在超微结构水平上，一个独特的类型之间的相互作用的幼稚T淋巴细胞和肝实质细胞在体内。这些结果对病毒性肝炎的发病机制有一定的影响，其中肝细胞可能是主要的抗原呈递细胞，淋巴细胞通过肝脏时免疫耐受的发展也有一定的影响。
The liver has an established ability to induce tolerance. Recent evidence indicates that this unique property might be related to its distinctive architecture allowing T cells to be activated in situ independently of lymphoid tissues. Unlike lymph node-activated T cells, liver-activated T cells are shortlived, a mechanism that might contribute to the "liver tolerance effem" Although the potential role of hepatocytes as tolerogenic antigen-presenting cells has been demonstrated, the question as to whether these cells are able to interact with CD8(+) T cells in physiological settings remains controversial. Contradicting the immunological dogma stating that naive T lymphocytes are prevented from interacting with parenchymal cells within non-lymphoid organs by an impenetrable endothelial barrier, we show here that the unique morphology of the liver sinusoidal endothelial cell (I-SEC) permits interactions between lymphocytes and hepatocytes. Using electron microscopy, we demonstrate that liver resident lymphocytes as well as circulating naive CD8(+) T cells make direct contact with hepatocytes through cytoplasmic extensions penetrating the endothelial fenestrations that perforate the LSECs. Furthermore, the expression of molecules required for primary T cell activation, MHC class I and ICAM-1, is polarized on hepatocytes to the perisinusoidal cell membrane, thus maximizing the opportunity for interactions with circulating lymphocytes. In conclusion, this study has identified, at the ultrastructural level, a unique type of interaction between nave T lymphocytes and liver parenchymal cells in vivo. These results hold implications for the pathogenesis of viral hepatitis in which hepatocytes may represent the main antigen-presenting cell, and for the development of immune tolerance as lymphocytes pass through the liver.