Interleukin (IL)-2 and IL-12 fail to restore antibody-dependent cellular cytotoxicity (ADCC) of mononuclear cellS (MNC) from HIV-infected patients

MNC from HIV-infected patients have defective natural killer (NK) cell function as well as decreased IL-2 and IL-12 production. IL-2 and 11-12 are reported to partially correct this impaired NK activity found in vitro. We assessed the ability of these cytokines to enhance ADCC activity in HIV patients. Blood was obtained from normal adult controls and HIV+ patients (ages 5-34; mean 17.2 yrs) from the outpatient clinic. ADCC was assessed by 4-hour chromium⁵¹ release using CEM ^NKR (NK resistant) cells coated with the HIV gp-120 protein as target and HIV hyperimmune intravenous immunoglobulin (HMG) as antibody. NK activity was determined in the absence of antibody, and the effector :target ratio was 25:1. The cytokines were added to the wells and incubated with cells for 18 hours before the target cells were added. TABLE: PERCENT LYSIS OF HIV gp-120 COATED CEM CELLS Cytokines Control MNC (n=5) HIV (+) Patients (n=10) NK ADCC NK ADCC None 4.2±0.5 25.9±5.0 7.0±1.8 6.3±1.5 IL-2 (100 u/ml) 8.9±1.9 32.1±5.2 14.5±3.2 * 6.3±1.7 IL-12 (1 ng/ml) 10.1±2.3 * 32.0±3.1 15.8±4.3 * 5.4±1.4 IL-2 + IL-12 17,7±4.6 * 29.5±1.8 21.8±4.2 ** 7.0±1.8 * p < 0.05 / ** p < 0.001 compared to no cytokines. The NK activity of the HIV patients against the NK-resistant target was slightly higher than that of controls, and the NK activity of both control and patient MNC could be greatly increased by IL-2 and IL-12, with the combination of both producing the greatest cytotoxicity. NK activity using K562 targets was increased in both centrals and patients to a similar degree with IL-2 and IL-12. However, HIV-infected patients ware greatly deficient in ADCC function compared to normal adults, with little effect of IL-2 or IL-12. Thus, this defect in ADCC in the MNC of HIV patients appears recalcitrant to corrections by IL-2 and IL-12 despite improvement in NK activity with these same agents.