Antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer(NK) and lymphokine activated killer cells may be important in host defense against HIV infection. We studied the ability of HIVIG to arm resting and cytokine-stimulated mononuclear cells (MNC) in vitro to specifically kill HIV target cells. MNC from normal adults were preincubated in media only (control) and media with interleukin-2 (IL-2, 100u/ml) and IL-12 (1ng/ml) at 37°C for 18 hours. MNC were next incubated with HIVIG (1 mg/ml) with or without 12% polyethelene glycol (PEG, MW:10,000) for 90 minutes on ice and then washed 3 times. ADCC was assessed by 4-hour 51Cr release using CEM.NKR cells coated with HIV gp120 (MN) as targets with HIVIG as antibody. NK activity was determined in the absence of soluble HIVIG. Gp120-specific CMC, a measure of HIVIG-directed killing dependent on cytophilic antibody, was obtained by subtracting the cytotoxicity of uncoated CEM.NKR cells from that of gp120-coated CEM-NKR cells. Table

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IL-2 and IL-12 augmented NK activity, down-regulated ADCC, but had little effect on gp120-specific CMC. Arming with HIVIG increased CMC in both control and cytokine-stimulated MNC. HIVIG plus PEG further enhanced CMC with concomitant suppression of ADCC whereas PEG alone had little effect(not shown). The results indicate that arming MNC in vitro with HIVIG and PEG facilitate their targeting of HIV-infected cells, and may be of value in adoptive immunotherapy in HIV disease.