Peripheral loss of CD8+CD161++TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients

Barathan, M. and Mohamed, R. and Vadivelu, J. and Chang, L.Y. and Saeidi, A. and Yong, Y.K. and Ravishankar Ram, M. and Gopal, K. and Velu, V. and Larsson, M. and Shankar, E.M. (2016) Peripheral loss of CD8+CD161++TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients. European Journal of Clinical Investigation, 46 (2). pp. 170-180. ISSN 0014-2972

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Official URL: https://doi.org/10.1111/eci.12581

Abstract

Background: Mucosal-associated invariant T (MAIT) cells play an important role in innate host defence. MAIT cells appear to undergo exhaustion and are functionally weakened in chronic viral infections. However, their role in chronic hepatitis C virus (HCV) infection remains unclear. Materials and methods: We investigated the frequency of CD8+CD161++TCR Vα7.2+ MAIT cells in a cross-sectional cohort of chronic HCV-infected patients (n = 25) and healthy controls (n = 25). Peripheral blood mononuclear cells were investigated for circulating MAIT cell frequency, liver-homing (CCR5 and CD103), biomarkers of immune exhaustion (PD-1, TIM-3 and CTLA-4), chronic immune activation (CD38 and HLA-DR), and immunosenescence (CD57) by flow cytometry. Results: The frequency of MAIT cells was significantly decreased, and increased signs of immune exhaustion and chronic immune activation were clearly evident on MAIT cells of HCV-infected patients. Decrease of CCR5 on circulating MAIT cells is suggestive of their peripheral loss in chronic HCV-infected patients. MAIT cells also showed significantly increased levels of HLA-DR, CD38, PD-1, TIM-3 and CTLA-4, besides CD57 in chronic HCV disease. Conclusions: Immune exhaustion and senescence of CD8+CD161++TCR Vα7.2+ MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression.

Item Type: Article
Uncontrolled Keywords: CD38; Exhaustion; HCV infection; MAIT cells; PD-1; TCRVα7.2
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 07 Dec 2017 01:53
Last Modified: 07 Dec 2017 01:53
URI: http://eprints.um.edu.my/id/eprint/18463

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