CMV infection of human sinusoidal endothelium regulates hepatic T cell recruitment and activation

Journal of Hepatology
Tony BrunsDavid H Adams

Abstract

Human cytomegalovirus infection (HCMV) is associated with an increased morbidity after liver transplantation, by facilitating allograft rejection and accelerating underlying hepatic inflammation. We hypothesized that human hepatic sinusoidal endothelial cells infected with HCMV possess the capacity to modulate allogeneic T cell recruitment and activation, thereby providing a plausible mechanism of how HCMV infection is able to enhance hepatic immune activation. Human hepatic sinusoidal endothelial cells were isolated from explanted livers and infected with recombinant endotheliotropic HCMV. We used static and flow-based models to quantify adhesion and transendothelial migration of allogeneic T cell subsets and determine their post-migratory phenotype and function. HCMV infection of primary human hepatic sinusoidal endothelial cells facilitated ICAM-1 and CXCL10-dependent CD4 T cell transendothelial migration under physiological levels of shear stress. Recruited T cells were primarily non-virus-specific CXCR3(hi) effector memory T cells, which demonstrated features of LFA3-dependent Th1 activation after migration, and activated regulatory T cells, which retained a suppressive phenotype following transmigration. The ability of in...Continue Reading

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Citations

Jul 18, 2016·Journal of Hepatology·Johanne PoissonPierre-Emmanuel Rautou
May 16, 2017·Current Opinion in Infectious Diseases·Shigeo FujiMarkus Kapp
Dec 16, 2017·Nature Immunology·Janko Nikolich-Žugich
May 31, 2018·Nature Reviews. Gastroenterology & Hepatology·Shishir ShettyDavid H Adams
Nov 22, 2016·Clinical & Translational Immunology·Yik Chun WongPatrick Bertolino
Mar 17, 2018·Frontiers in Immunology·Nicolle H R LitjensJaap Kwekkeboom
Apr 25, 2018·Proceedings of the National Academy of Sciences of the United States of America·Eddie C Y WangPeter Tomasec
Sep 26, 2017·Oncology Letters·Aitor BenedictoBeatriz Arteta
Feb 17, 2021·Nature Reviews. Gastroenterology & Hepatology·Jordi Gracia-SanchoRubén Francés
Feb 20, 2021·Journal of Clinical and Translational Hepatology·Teresa Da Cunha, George Y Wu

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