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Liver Int. 2018 Mar;38(3):458-468. doi: 10.1111/liv.13544. Epub 2017 Sep 16.

Mucosal-associated invariant T-cell frequency and function in blood and liver of HCV mono- and HCV/HIV co-infected patients with advanced fibrosis.

Author information

1
Department of Gastroenterology and Hepatology, Infectious Diseases Section, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
2
Department of Internal Medicine, Infectious Diseases Section, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
3
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
4
Department of Medicine, University Medical Center, Hamburg-Eppendorf, Germany.

Abstract

BACKGROUND & AIMS:

Mucosal-associated invariant T (MAIT) cells are important innate T cells with antimicrobial and immunoregulatory activity, recently found to be depleted in blood of patients with HIV and HCV mono-infections. In this study, we assessed the impact of HIV, HCV and HCV/HIV co-infection on circulating and intrahepatic MAIT-cells and correlations with liver fibrosis.

METHODS:

In this cross-sectional study, nine healthy subjects, nine HIV, 20 HCV and 22 HCV/HIV co-infected patients were included. Blood and liver fine needle aspirate biopsies were studied using flowcytometry for CD3+ CD161+ Vα7.2+ MAIT-cell frequency, phenotype and function in HCV mono-infected and HCV/HIV co-infected patients without or with mild fibrosis (Metavir-score F0-F1) or severe fibrosis to cirrhosis (Metavir-score F3-F4).

RESULTS:

Circulating MAIT-cells were decreased in blood of HCV, HIV and HCV/HIV patients with F0-F1. In HCV/HIV co-infected individuals with severe fibrosis to cirrhosis, the frequency of circulating MAIT-cells was even further depleted, whereas their function was comparable to HCV/HIV co-infected patients with low or absent fibrosis. In contrast, in HCV mono-infected patients, MAIT-cell frequencies were not related to fibrosis severity; however, MAIT-cell function was impaired in mono-infected patients with more fibrosis. More advanced liver fibrosis in HCV or HCV/HIV-infected patients was not reflected by increased accumulation of MAIT-cells in the affected liver.

CONCLUSIONS:

Severe liver fibrosis is associated with dysfunctional MAIT-cells in blood of HCV mono-infected patients, and lower MAIT frequencies in blood of HCV/HIV co-infected patients, without evidence for accumulation in the liver.

KEYWORDS:

fibrosis; hepatitis C virus; human immunodeficiency virus; mucosal-associated invariant T cell

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