Selective impairment of alpha-interferon-mediated natural killer augmentation in Sjögren's syndrome: differential effects of alpha-interferon, gamma-interferon, and interleukin 2 on cytolytic activity

Abstract

Natural killer (NK) function has been shown to be impaired in several autoimmune diseases including Sjögren's syndrome (SS). In the present study, in vitro effects of alpha-interferon (alpha-IFN), gamma-IFN and interleukin 2 (IL-2) on the NK cell activity were examined to analyse the regulatory system of NK-augmentation in patients with SS. The responsiveness of NK cell activity to alpha-IFN was markedly depressed in SS patients compared with normal controls, whereas the responsiveness to gamma-IFN was within normal limits. This is the first demonstration of the selective hyporesponsiveness of NK cell activity to one type of IFN in a certain disease. In addition, the kinetics study of NK-augmentation in normal donors revealed that alpha-IFN enhanced NK cell activity with a faster profile than gamma-IFN. These findings imply substantial differences between the two types of IFN in their mechanisms for enhancing NK cell activity, which deserve attention in evaluating the effects of IFNs. The present study also demonstrated that IL-2 could induce significantly higher levels of NK cell activity than alpha-IFN or gamma-IFN in SS and that this enhancing effect was almost comparable to that in normal controls. Thus, there seem to be multiple regulatory mechanisms for enhancement of NK cell activity, and a portion of the mechanisms may be selectively impaired in certain human diseases such as SS. The selective hyporesponsiveness to alpha-IFN could be relevant to the idea of viral participation in pathogenesis of SS.