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T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells

细胞生物学 生物 细胞毒性T细胞 CD8型 肝细胞学 T细胞 抗原提呈细胞 内皮干细胞 抗原 免疫学 免疫系统 体外 内分泌学 生物化学 肝脏代谢
作者
Alessandra Warren,David G. Le Couteur,Robin Fraser,David G. Bowen,Geoffrey W. McCaughan,Patrick Bertolino
出处
期刊:Hepatology [Wiley]
卷期号:44 (5): 1182-1190 被引量:311
标识
DOI:10.1002/hep.21378
摘要

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 short-lived, a mechanism that might contribute to the "liver tolerance effect." 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 naïve 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 (LSEC) permits interactions between lymphocytes and hepatocytes. Using electron microscopy, we demonstrate that liver resident lymphocytes as well as circulating naïve 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 naïve 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.
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