NKp30⁺ NK cells are associated with HBV control during pegylated-interferon-alpha-2b therapy of chronic hepatitis B.

ABSTRACT: A pressing need exists for improved therapeutic options for chronic hepatitis B (CHB). Pegylated-interferon-alpha (Peg-IFN-?) achieves sustained off-treatment responses in many cases because of its direct anti-viral effects and regulation of the immune response. However, non-responsiveness to Peg-IFN-? is frequent, and the mechanism is poorly understood. In this study, we found that the frequency and absolute number of NKp30⁺ natural killer (NK) cells increased markedly, accompanied by enhanced CD107a and IFN-? production, during Peg-IFN-?-2b monotherapy or combination therapy with adefovir dipivoxil in patients with CHB, especially in responders. The responders and non-responders differed in the frequency of polyfunctional IFN-?⁺ CD107⁺ NK cells. In addition, the increase in NKp30⁺ NK cells was negatively correlated with the HBV viral load and plasma HBeAg. Moreover, it was found that IL-15 may contribute to the up-regulation of NKp30 on the NK cells, and this up-regulation was not induced in vitro by Peg-IFN-?-2b alone. However, in the non-responders, these NKp30⁺ NK cells were dysfunctional because of increased NKG2A expression, which partly explains the inactivation of NKp30⁺ NK cells and the reduced capacity of these cells to produce antiviral cytokines. These findings may provide a new mechanism to explain the variable efficacy of Peg-IFN-?-2b therapy.

SUBMITTER: Shen X 

PROVIDER: S-EPMC5150634 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature