Liver environment and HCV replication affect human T-cell phenotype and expression of inhibitory receptors

DC Kroy, D Ciuffreda, JH Cooperrider, M Tomlinson… - Gastroenterology, 2014 - Elsevier
DC Kroy, D Ciuffreda, JH Cooperrider, M Tomlinson, GD Hauck, J Aneja, C Berger, D Wolski
Gastroenterology, 2014Elsevier
Background & Aims There is an unclear relationship between inhibitory receptor expression
on T cells and their ability to control viral infections. Studies of human immune cells have
been mostly limited to T cells from blood, which is often not the site of infection. We
investigated the relationship between T-cell location, expression of inhibitory receptors,
maturation, and viral control using blood and liver T cells from patients with hepatitis C virus
(HCV) and other viral infections. Methods We analyzed 36 liver samples from HCV antibody …
Background & Aims
There is an unclear relationship between inhibitory receptor expression on T cells and their ability to control viral infections. Studies of human immune cells have been mostly limited to T cells from blood, which is often not the site of infection. We investigated the relationship between T-cell location, expression of inhibitory receptors, maturation, and viral control using blood and liver T cells from patients with hepatitis C virus (HCV) and other viral infections.
Methods
We analyzed 36 liver samples from HCV antibody–positive patients (30 from patients with chronic HCV infection, 5 from patients with sustained virological responses to treatment, and 1 from a patient with spontaneous clearance) with 19 paired blood samples and 51 liver samples from HCV-negative patients with 17 paired blood samples. Intrahepatic and circulating lymphocytes were extracted; T-cell markers and inhibitory receptors were quantified for total and virus-specific T cells by flow cytometry.
Results
Levels of the markers PD-1 and 2B4 (but not CD160, TIM-3, or LAG-3) were increased on intrahepatic T cells from healthy and diseased liver tissues compared with T cells from blood. HCV-specific intrahepatic CD8+ T cells from patients with chronic HCV infection were distinct in that they expressed TIM-3 along with PD-1 and 2B4. In comparison, HCV-specific CD8+ T cells from patients with sustained virological responses and T cells that recognized cytomegalovirus lacked TIM-3 but expressed higher levels of LAG-3; these cells also had different memory phenotypes and proliferative capacity.
Conclusions
T cells from liver express different inhibitory receptors than T cells from blood, independent of liver disease. HCV-specific and cytomegalovirus-specific CD8+ T cells can be differentiated based on their expression of inhibitory receptors; these correlate with their memory phenotype and levels of proliferation and viral control.
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