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.