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

摘要

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 CD 3 + CD 161 + 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.