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

被引:210
作者
Warren, Alessandra
Le Couteur, David G.
Fraser, Robin
Bowen, David G.
McCaughan, Geoffrey W.
Bertolino, Patrick
机构
[1] Univ Sydney, Sydney, NSW 2006, Australia
[2] CERA, Sydney, NSW, Australia
[3] Concord RG Hosp, ANZAC Res Inst, Sydney, NSW, Australia
[4] Univ Otago, Christchurch Sch Med & Hlth Sci, Dept Pathol, Christchurch, New Zealand
[5] Columbus Childrens Res Inst, Ctr Vaccine & Immun, Columbus, OH USA
[6] Royal Prince Alfred Hosp, Centenary Inst Canc Med & Cell Biol, AW Morrow Gastroenterol & Liver Ctr, Sydney, NSW, Australia
关键词
D O I
10.1002/hep.21378
中图分类号
R57 [消化系及腹部疾病];
学科分类号
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 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.
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页码:1182 / 1190
页数:9
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