Evaluation of natural killer cell activity

The immune response to a virus infection involves both nonspecific and specific immune mechanisms. Natural killer (NK) cells are naturally-occurring cytolytic cells capable of lysing various tumor cells and virus-infected cells without previous sensitization or with a requirement for major histocompatibility (MHC) restriction. The molecular mechanisms that explain how NK cells are able to kill virus-infected cells and tumor cells while sparing self-cells have recently been elucidated (1). NK cells may play a role as a first line of defense against virus infection by mediating lysis of virus-infected cells prior to the development of specific humoral and cell-mediated defense mechanisms. Although the percentage of NK cells in HIV-1-infected patients may remain normal, the absolute numbers of some NK subsets are substantially reduced in the blood of HIV-1 patients and NK function decreases as HIV-1 infection proceeds (2-4). The interplay between NK cells and other cells of the innate and specific immune system is mediated, in part, through the release of cytokines, in particular interleukin-2 (IL-2) and γ-interferon (γ-IFN). Thus, it seems plausible that the generalized immunosuppression seen in HIV-1-infected patients may contribute to the impairment of NK activity. A dynamic balance between NK cells and cytotoxic T lymphocytes (CTL) is likely to occur (5). Therefore, any alterations in NK or CTL activity are likely to impair anti-HIV-1 cytolytic function.