CD56^+dim and CD56^+bright cell activation and apoptosis in hepatitis C virus infection

CD3^-CD56^+dim natural killer (NK) cells, which are cytotoxic against virally infected cells, may be important in hepatitis C virus (HCV)-infected patients who are successfully treated with pegylated interferon (PEG-IFN)-α. We used flow cytometry to enumerate activated (CD69 ⁺) and apoptotic (annexin-V⁺) dim (CD3 ^-CD56^+dim) and bright (CD3^-CD56 ^+bright) NK cells obtained from HCV-infected patients before treatment (n = 16) and healthy controls (n = 15) in the absence and presence of pegylated interferon (PEG-IFN)-α-2b. A subset of HCV-infected patients, subsequently treated with PEG-IFN-α-2b in vivo, was determined to have a sustained virological response (SVR, n = 6) or to not respond (NR) to treatment (n = 5). In the absence of IFN, activated dim (CD3^-CD56 ^+dimCD69⁺) NK cells were significantly decreased (P = 0.04) while activated apoptotic dim (CD3^-CD56^+dimCD69 ⁺annexin-V⁺) NK cells tended to be increased (P = 0.07) in SVR patients compared with NR patients. Activated bright (CD3 ^-CD56^+brightCD69⁺) and activated apoptotic bright (CD3^-CD56^+brightCD69⁺annexin-V ⁺) NK cells were significantly correlated (P = 0.02 and P = 0.01, respectively) with increasing hepatic inflammation. These findings suggest that in the absence of PEG-IFN, activated dim (CD3^-CD56 ^+dimCD69⁺) NK cell turnover may be enhanced in SVR compared with NR patients and that activated bright (CD3^- CD56 ^+brightCD69⁺) NK cells may play a role in liver inflammation.