Abstract
ObjectiveMucosal-associated invariant T (MAIT) cells comprise a subpopulation of T cells that can be activated by bacterial products and cytokines to produce IFN-γ. Since little is known on MAIT cells during HCV infection, we compared their phenotype and function in comparison to HIV and HCV/HIV co-infected patients, and determined the effect of IFN-α-based and direct-acting antiviral therapy on MAIT cells of HCV patients.MethodsBlood samples from patients with chronic HCV (CHCV), virologically suppressed HIV, acute HCV/HIV co-infection (AHCV/HIV) and healthy individuals were examined by flowcytometry for phenotype and function of MAIT and NK cells.Results and ConclusionsCompared to healthy individuals, the frequency of CD161+Vα7.2+ MAIT cells was significantly decreased in patients with CHCV, HIV and AHCV/HIV co-infection. CD38 expression on MAIT cells was increased in AHCV/HIV patients. MAIT cells were responsive to IFN-α in vitro as evidenced by enhanced frequencies of IFN-γ producing cells. IFN-α-based therapy for CHCV decreased the frequency of IFN-γ+ MAIT cells, which was still observed 24 weeks after successful therapy. Importantly, even after successful IFN-α-based as well as IFN-α-free therapy for CHCV, decreased frequencies of MAIT cells persisted. We show that the frequencies of MAIT cells are reduced in blood of patients with CHCV, HIV and in AHCV/HIV co-infection compared to healthy individuals. Successful therapy for CHCV did not normalize MAIT cell frequencies at 24 weeks follow up. The impact of HIV and HCV infection on the numbers and function of MAIT cells warrant further studies on the impact of viral infections and the antimicrobial function of MAIT cells.
Highlights
Following infection with hepatitis C virus (HCV), hepatocytes are triggered to produce type I and III interferons (IFN), which induce the expression of hundreds of IFN stimulating genes (ISG) with anti-viral activity [1,2,3]
We show that the frequencies of Mucosal-Associated Invariant T (MAIT) cells are reduced in blood of patients with chronic HCV (CHCV), human immunodeficiency virus (HIV) and in AHCV/ HIV co-infection compared to healthy individuals
MAIT cells are decreased in patients with chronic HCV, HIV and AHCV/ HIV co-infection compared to healthy controls
Summary
Following infection with hepatitis C virus (HCV), hepatocytes are triggered to produce type I and III interferons (IFN), which induce the expression of hundreds of IFN stimulating genes (ISG) with anti-viral activity [1,2,3]. MAIT cells are reduced in peripheral blood and lymph nodes of patients with chronic HIV infection, and their cytokine production and cytolytic functions are severely affected which has been suggested to be the result of exhaustion. It has been suggested that the functional impairment and numerical decline of MAIT cells contributes to the high incidence of bacterial infections observed in HIV patients [18]. At the moment it is unclear what causes the depletion of MAIT cells in HIV infection. Similar findings were reported recently in patients chronically infected with HCV where the MAIT cell numbers in blood were severely reduced during persistent infection [23]. In chronic HCV, successful HCV clearance by IFN-free therapy does not result in normalization of MAIT cell numbers
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