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Human hepatic stellate cells show features of antigen‐presenting cells and stimulate lymphocyte proliferation

Human hepatic stellate cells show features of antigen‐presenting cells and stimulate lymphocyte... Following cell activation, hepatic stellate cells (HSCs) acquire proinflammatory and profibrogenic properties. We investigated whether activated HSCs also display immune properties. Here we show that cultured human HSCs express membrane proteins involved in antigen presentation, including members of the HLA family (HLA‐I and HLA‐II), lipid‐presenting molecules (CD1b and CD1c), and factors involved in T‐cell activation (CD40 and CD80). Exposure of HSCs to proinflammatory cytokines markedly up‐regulates these molecules. Importantly, cells freshly isolated from human cirrhotic livers (in vivo activated HSCs) highly express HLA‐II and CD40, suggesting that HSCs can act as antigen‐presenting cells (APCs) in human fibrogenesis. We also explored whether human HSCs can efficiently process exogenous antigens. Activated HSCs internalize low‐ and high‐molecular‐weight dextran and transferrin, indicating that they can perform fluid‐phase and receptor‐mediated endocytosis. Moreover, HSCs can perform phagocytosis of macromolecules because they internalize latex particles as well as bacteria. Interestingly, both culture‐activated and in vivo activated HSCs express high levels of CD68, a protein involved in antigen trafficking. Finally, we studied whether HSCs modulate T‐lymphocyte proliferation. In basal conditions, coculture of irradiated HSCs barely induces allogeneic T‐lymphocyte proliferation. However, cytokine‐stimulated HSCs stimulate the allogeneic T‐lymphocyte response in an HLA‐II—dependent manner. In conclusion, human activated HSCs express molecules for antigen presentation, internalize macromolecules, and modulate T‐lymphocyte proliferation. These results suggest that HSCs may play a role in the immune function of the liver. (Hepatology 2003;38:919–929). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Hepatology Wolters Kluwer Health

Human hepatic stellate cells show features of antigen‐presenting cells and stimulate lymphocyte proliferation

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Human hepatic stellate cells show features of antigen‐presenting cells and stimulate lymphocyte proliferation

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References (57)

Publisher
Wolters Kluwer Health
Copyright
Copyright © 2003 Wiley Subscription Services
ISSN
0270-9139
eISSN
1527-3350
DOI
10.1002/hep.1840380418
Publisher site
See Article on Publisher Site

Abstract

Following cell activation, hepatic stellate cells (HSCs) acquire proinflammatory and profibrogenic properties. We investigated whether activated HSCs also display immune properties. Here we show that cultured human HSCs express membrane proteins involved in antigen presentation, including members of the HLA family (HLA‐I and HLA‐II), lipid‐presenting molecules (CD1b and CD1c), and factors involved in T‐cell activation (CD40 and CD80). Exposure of HSCs to proinflammatory cytokines markedly up‐regulates these molecules. Importantly, cells freshly isolated from human cirrhotic livers (in vivo activated HSCs) highly express HLA‐II and CD40, suggesting that HSCs can act as antigen‐presenting cells (APCs) in human fibrogenesis. We also explored whether human HSCs can efficiently process exogenous antigens. Activated HSCs internalize low‐ and high‐molecular‐weight dextran and transferrin, indicating that they can perform fluid‐phase and receptor‐mediated endocytosis. Moreover, HSCs can perform phagocytosis of macromolecules because they internalize latex particles as well as bacteria. Interestingly, both culture‐activated and in vivo activated HSCs express high levels of CD68, a protein involved in antigen trafficking. Finally, we studied whether HSCs modulate T‐lymphocyte proliferation. In basal conditions, coculture of irradiated HSCs barely induces allogeneic T‐lymphocyte proliferation. However, cytokine‐stimulated HSCs stimulate the allogeneic T‐lymphocyte response in an HLA‐II—dependent manner. In conclusion, human activated HSCs express molecules for antigen presentation, internalize macromolecules, and modulate T‐lymphocyte proliferation. These results suggest that HSCs may play a role in the immune function of the liver. (Hepatology 2003;38:919–929).

Journal

Hepatology – Wolters Kluwer Health

Published: Jan 1, 2003

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