BACKGROUND: During the early phases of a hepatitis C virus (HCV) infection, NK cell activation appears to be critical to the induction of adaptive immune responses that have the potential of clearing the infection. This study aimed to investigate the phenotype and function of NK cells in chronic HCV (CHC) patients, particularly patients who cleared HCV infections spontaneously (SR-HCV). MATERIAL AND METHODS: Peripheral blood NK cells were compared between 36 CHC patients, 12 SR-HCV patients, and 14 healthy controls (HC). The phenotype and function of NK cells were characterized by flow cytometry. In addition, the potential associations between the frequency of NK cell subsets and ALT, AST and HCV viral loads were also analyzed. RESULTS: Our data revealed that the population of CD3-CD56+ NK cells was significantly decreased in CHC and SR-HCV patients compared to levels in HC (P = 0.031, P = 0.014). Interestingly, we found that the levels of the CD158b inhibitory receptor were higher in CHC patients compared to levels observed in HCand SR-HCV subjects (P = 0.018, P = 0.036). In addition, the percentages of the activation receptors NKp30 and NKp46 were significantly decreased in CHC and SR-HCV patients compared to their expression levels in HC (P < 0.05). Moreover, the frequencies of inducible CD107a (but not IFN-γ-secreting) NK cellsfrom both CHC and SR-HCV patients were significantly lower than frequencies observed in controls (P = 0.018, P = 0.027). CONCLUSION: Our data indicated that the higher frequency of inhibitory NK cells combined with fewer activated NK cells may be associated with HCV-related chronic inflammation involved in CHC pathogenesis.
BACKGROUND: During the early phases of a hepatitis C virus (HCV) infection, NK cell activation appears to be critical to the induction of adaptive immune responses that have the potential of clearing the infection. This study aimed to investigate the phenotype and function of NK cells in chronic HCV (CHC) patients, particularly patients who cleared HCV infections spontaneously (SR-HCV). MATERIAL AND METHODS: Peripheral blood NK cells were compared between 36 CHCpatients, 12 SR-HCVpatients, and 14 healthy controls (HC). The phenotype and function of NK cells were characterized by flow cytometry. In addition, the potential associations between the frequency of NK cell subsets and ALT, AST and HCV viral loads were also analyzed. RESULTS: Our data revealed that the population of CD3-CD56+ NK cells was significantly decreased in CHC and SR-HCVpatients compared to levels in HC (P = 0.031, P = 0.014). Interestingly, we found that the levels of the CD158b inhibitory receptor were higher in CHCpatients compared to levels observed in HCand SR-HCV subjects (P = 0.018, P = 0.036). In addition, the percentages of the activation receptors NKp30 and NKp46 were significantly decreased in CHC and SR-HCVpatients compared to their expression levels in HC (P < 0.05). Moreover, the frequencies of inducible CD107a (but not IFN-γ-secreting) NK cellsfrom both CHC and SR-HCVpatients were significantly lower than frequencies observed in controls (P = 0.018, P = 0.027). CONCLUSION: Our data indicated that the higher frequency of inhibitory NK cells combined with fewer activated NK cells may be associated with HCV-related chronic inflammation involved in CHC pathogenesis.
Authors: Mark Hatherill; Thomas J Scriba; Sara Suliman; Hennie Geldenhuys; John L Johnson; Jane E Hughes; Erica Smit; Melissa Murphy; Asma Toefy; Lesedi Lerumo; Christiaan Hopley; Bernadette Pienaar; Phalkun Chheng; Elisa Nemes; Daniel F Hoft; Willem A Hanekom; W Henry Boom Journal: J Immunol Date: 2016-07-13 Impact factor: 5.422