Human immunodeficiency virus (HIV) type-1 GP120-specific cell-mediated cytotoxicity (CMC) and natural killer (NK) activity in HIV-infected (HIV⁺) subjects: Enhancement with interleukin-2(IL-2), IL-12, and IL-15

Cell-mediated cytotoxicity (CMC), as mediated by cytophilic antibody to human immunodeficiency virus (HIV) antigens, may be an important defense in HIV-infected (HIV⁺) patients in response to the virus. In this study the ability of interleukin (IL)-2, IL-12, and IL-15 to enhance natural killer (NK) and gp120-specific CMC of mononuclear cells (MNCs) from HIV⁺ children and adults was examined. NK activity against K562 cells was deficient in HIV⁺ patients compared to controls and could be enhanced by IL-2, IL-12, or IL-15, with the combinations of IL-2 + IL-12 and IL-12 + IL-15 producing more cytotoxicity than individual cytokines. Gp120-specific CMC was significantly higher in patients than in controls. It could be increased by IL-2, IL-12, and IL-15 and further by combining IL-2 and IL-12. When an exogenous source of antibody in the form of hyperimmune HIV-specific immunoglobulin (HIVIG) was present, the response of control MNCs was much higher than that of patients, although gp120-specific cytotoxicity of patients' MNCs was significantly enhanced (two- to threefold) by the addition of HIVIG. This increment in cytotoxicity due to HIVIG, however, could not be further augmented by cytokines in controls or patients. Our findings suggest multiple cytokine administration to boost NK cell function, together with passive immunotherapy, might offer a new therapeutic approach to benefit HIV⁺ patients.