Adaptive Natural Killer Cell Functional Recovery in Hepatitis C Virus Cured Patients
- 1 January 2021
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 73 (1), 79-90
- https://doi.org/10.1002/hep.31273
Abstract
Background and Aims Current evidence suggests that dysfunctional natural killer (NK) cell responses during hepatitis C virus (HCV) infection can be restored after viral eradication with direct acting antivirals (DAAs). However, the fate of the recently described adaptive NK cell population, endowed with increased ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC), during HCV infection is poorly defined, while no study has explored the effects of DAAs on this NK subset. Approach and Results We performed multicolor flow cytometry to investigate CD57(+) Fc epsilon RI gamma(neg) adaptive and Fc epsilon RI gamma(pos) conventional NK cell phenotype and function before and after DAA treatment in 59 patients chronically infected with HCV, 39 with advanced liver fibrosis, and 20 with mild-moderate liver fibrosis. Moreover, bulk NK cell phenotype and function were analyzed after cytokine activation following contact with K562 target cells. The proportion of Fc epsilon RI gamma(neg) NK cells in patients with HCV was associated with increased HCV load at baseline, and it was significantly reduced after treatment. Patients with an advanced fibrosis stage displayed increased NK cell activation and exhaustion markers that normalized after therapy. Of note, adaptive NK cells from patients with HCV were characterized by increased programmed death receptor 1 expression and reduced ADCC activity at baseline. DAA treatment restored ADCC ability and reduced programmed death receptor 1 expression. Conclusions HCV profoundly affects the frequency, phenotype, and function of adaptive NK cells. DAA therapy restores a normal adaptive NK phenotype and enhances interferon-gamma production by this cell subset.This publication has 28 references indexed in Scilit:
- Identification of human NK cells that are deficient for signaling adaptor FcRγ and specialized for antibody-dependent immune functionsInternational Immunology, 2012
- Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent functionBlood, 2012
- Decreased NKp46 and NKG2D and elevated PD‐1 are associated with altered NK‐cell function in pediatric transplant patients with PTLDEuropean Journal of Immunology, 2011
- Unconventional Repertoire Profile Is Imprinted during Acute Chikungunya Infection for Natural Killer Cells Polarization toward CytotoxicityPLoS Pathogens, 2011
- Expansion of a unique CD57+ NKG2Chi natural killer cell subset during acute human cytomegalovirus infectionProceedings of the National Academy of Sciences of the United States of America, 2011
- Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirusThe Journal of Experimental Medicine, 2010
- The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti–PD-1 antibodyBlood, 2010
- Natural Killer Cells Are Polarized Toward Cytotoxicity in Chronic Hepatitis C in an Interferon-Alfa–Dependent MannerGastroenterology, 2010
- Chronic HIV-1 viremia reverses NKG2A/NKG2C ratio on natural killer cells in patients with human cytomegalovirus co-infectionAIDS, 2010
- Natural Killer Cell Functional Dichotomy in Chronic Hepatitis B and Chronic Hepatitis C Virus InfectionsGastroenterology, 2009