EFFECT OF INTERLEUKIN (IL)-12 AND IL-15 ON ACTIVATED NATURAL-KILLER (ANK) AND ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY (ADCC) IN HIV-INFECTION

The ability of IL-12 and IL-15 to enhance natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) of mononuclear ce lls (MNCs) from HIV+ children and their mothers was investigated. MNCs from HIV+ patients were deficient in NK and ADCC activity compared to control MNCs against several target cells. Overnight incubation with IL-15 or IL-12 augmented NK activity of MNCs from both patients and co ntrols, and the combination of IL-12 and IL-15 resulted in the greates t enhancement. ADCC in HIV+ patients against gp120-coated CEM.NKR cell s or chicken erythrocytes could also be enhanced by IL-2 or IL-15 in o vernight cultures. Culturing MNCs with either IL-2 or IL-15 for 1 week increased the NK activity in patients to levels of controls treated w ith these cytokines. However, the response to the combination of IL-12 and IL-15 was less than that to IL-15 alone in 1-week cultures. Cultu ring MNCs with IL-2 and IL-15 for 1 week also increased the percentage of CD16(+)/CD56(+) cells in both patients and controls. Thus, IL-15 c an restore the deficient NK activity in patients and may be a candidat e for immunomodulative therapy in HIV+ patients.