INTERLEUKIN-2 (IL-2) AND IL-12 ENHANCE HIV GP120-SPECIFIC CELL-MEDIATED CYTOTOXICITY (CMC) OF MONONUCLEAR CELLS FROM HIV-INFECTED(HIV+) PATIENTS.† 58

Antibody-dependent cellular cytotoxicity (ADCC) may be important in host defense against HIV. Gp120-specific CMC, mediated by natural killer (NK) cells armed in vivo with cytophilic antibody in HIV+ patients, may also represent a protective response. We assessed the ability of IL-2 and IL-12 to enhance ADCC and gp120-specific CMC in HIV+ patients. Blood was obtained from normal adults and HIV+ children and their HIV+ mothers from the outpatient clinic. ADCC was assessed by 4-hour ⁵¹Cr release using CEM.NKR cells coated with HIV gp120 (IIIB) as targets, and HIV hyperimmune intravenous immunoglobulin(HIVIG) as antibody. NK activity was determined in the absence of HIVIG. Gp120-specific CMC was obtained by subtracting the cytotoxicity of uncoated CEM.NKR cells from that of gp120-coated targets. The cytokines were incubated with effector cells for 18 hours before the target cells were added.Table

Table 1

HIV+ patients were greatly deficient in ADCC compared to controls, with little effect of IL-2 and IL-12. However, gp120-specific CMC of the HIV+ patients was significantly higher than that of controls, and could be markedly enhanced by cytokines. Thus, gp120-specific CMC, a form of direct ADCC dependent on cytophilic antibody in HIV+ patients, is IL-2 and IL-12 augmentable, while the defect in conventional ADCC appears recalcitrant to correction by IL-2 and IL-12.