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Natural killer (NK) cell function was investigated in Malaysian HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency. Some patients experienced immune restoration disease (IRD) presenting as exacerbations of pre-existing infections. Whilst most IRD are attributed to interferon-gamma (IFN?) produced by T-cells, NK cells may also contribute. Blood leukocytes were collected prospectively from 100 HIV patients over 1 year on ART, plus 36 healthy controls. Eleven patients who experienced an IRD and 14 matched controls were assayed. Cells producing IFN? were quantitated by ELISpot after stimulation with an NK target (K562 cells) or antigens from pathogens associated with the IRD. NK cell subsets, CD16 and perforin expression were determined by flow cytometry. NK cells profiles were restored on ART, but NK cell IFN? production remained impaired. Low CD16 expression on CD56lo NK cells may mark a predisposition for an IRD.
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