Differential alteration of CD56bright and CD56dim natural killer cells in frequency, phenotype, and cytokine response in chronic hepatitis C virus infection

Natural killer (NK) cells play an important role in immune responses to virus infection. The cell population consists of CD56(bright) (bright-subset) and CD56(dim) (dim-subset) subsets that possess armed functions of cytokine production and cytolysis, respectively. How these subsets are involved in chronic hepatitis C virus infection (CHC) remains obscure. We investigated the frequency, phenotype, and cytokine response of these subsets in blood from CHC patients and healthy subjects (HS). Dim-subset, but not bright-subset, showed lower frequency in the patients than in HS. Bright-subset from the patients more frequently expressed the NKG2A/CD94 inhibitory receptor than that from HS, while both subsets from the patients expressed lower levels of the NKG2D activating receptor. Both subsets from the patients displayed a significantly higher level of the signal transducer and activator of transcription (STAT) 1, compared with the HS. Upon stimulation with interferon-alpha, bright-subset activated less STAT4, required for interferon-gamma production, and dim-subset activated more STAT1, required for cytolysis, in the patients than in HS. These results indicate alterations of NK cell subsets in frequency, phenotype, and cytokine response in CHC, which might be associated with the immune pathogenesis of CHC.