Hepatitis C viral infection is associated with activated cytolytic natural killer cells expressing high levels of T cell immunoglobulin- and mucin-domain-containing molecule-3

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Lucy Golden-MasonHugo R Rosen

Abstract

T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) is an inhibitory receptor implicated in T cell exhaustion characteristic of chronic viral infection. Limited data exist on NK cell Tim-3 expression and functional consequences. In chronic hepatitis C virus (HCV)-infected subjects, we found increased Tim-3 on NKs, which was associated with an activated phenotype. The high level of Tim-3 was not reversed by successful IFN-alpha-based antiviral therapy. Tim-3(high) NK cells up-regulated TRAIL in response to IFN-alpha to a greater extent and demonstrated greater lymphokine-activated killing activity, viral control, and degranulation but similar cytokine production than their Tim-3(low) counterparts. Our results suggest that Tim-3 on NKs is associated with activation of this innate lymphocyte population that is polarized towards cytotoxicity in chronic HCV. These findings reveal roles for Tim-3 in the regulation of NKs that might represent targets for treatment of chronic viral infections.

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Citations

May 28, 2016·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·J P PeiK Jing
Jul 21, 2016·Scandinavian Journal of Gastroenterology·Hans Jakob HartlingSusanne Dam Nielsen
Jul 14, 2017·International Journal of Molecular Sciences·Hyosun ChoChang Wook Kim
Jul 10, 2020·Expert Opinion on Investigational Drugs·Danilo RoccoCesare Gridelli
Feb 24, 2016·World Journal of Gastroenterology : WJG·Yuan LiuChun-Hong Ma
Sep 12, 2017·Cellular & Molecular Immunology·Yanhong LiMeirong Du
Apr 21, 2018·Frontiers of Medicine·Meijuan ZhengZhigang Tian
Nov 18, 2018·Archivum Immunologiae Et Therapiae Experimentalis·Arkadiusz UrbanowiczMichał Ciszek
Feb 10, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhifang ChenJianbing Ding

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