Enhancement of Natural Killer Cell Activation and Antibody-Dependent Cellular Cytotoxicity by Interferon-αand Interleukin-12 in Vaginal Mucosae SIVmac251-InfectedMacaca fascicularis

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Abstract
We studied the innate immune system of Cynomolgus monkeys (Macaca fascicularis) experimentally infected via the vaginal mucosae with a virulent simian immunodeficiency virus isolate SIVmac251. Animals were evaluated for their natural killer (NK) cell activity, and for their antibody-dependent cellular cytotoxicity. NK cells from SIVmac251-infected macaques show impaired NK cell activity compared to cells from uninfected animals. Subsequent treatment of NK cells with interferon-α (IFN-α) or interleukin-12 (IL-12) alone partially restored the NK activity. However, either treatment of NK cells with both IFN-α and IL-12 completely reversed the impairment of cytotoxicity induced by simian immunodeficiency virus (SIV) infection. Incubation of NK cells from infected but not from uninfected monkeys with IFN-α and IL-12 for 8 days increased the percentage of CD16+/CD56+ cells twofold to fivefold and enhanced antibody-dependent cellular cytotoxicity (ADCC) activity. Thus IFN-α and IL-12 greatly enhance both the NK cell and ADCC activities of peripheral blood cells from SIVmac251-infected animals and increase the number of NK cells in longer term culture. The combined effect of IFN-α and IL-12 in enhancing NK cell activity may provide a novel therapeutic approach for the restoration of depressed NK cell activity observed in human immunodeficiency virus (HIV)-infected patients.