Loss of the CD56hiCD16 NK cell subset and NK cell interferon-γ production during antiretroviral therapy for HIV-1: partial recovery by human growth hormone

Authors

  • M. R. GOODIER,

    Corresponding author
    1. Department of Immunology, Imperial College London, Faculty of Medicine, Chelsea and Westminster Hospital, London, and
      Dr M. R. Goodier, Department of Immunology, Imperial College London, Faculty of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
      E-mail: m.goodier@ic.ac.uk
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  • N. IMAMI,

    1. Department of Immunology, Imperial College London, Faculty of Medicine, Chelsea and Westminster Hospital, London, and
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  • G. MOYLE,

    1. Department of HIV/GU Medicine, Chelsea and Westminster Hospital, London, UK
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  • B. GAZZARD,

    1. Department of HIV/GU Medicine, Chelsea and Westminster Hospital, London, UK
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  • F. GOTCH

    1. Department of Immunology, Imperial College London, Faculty of Medicine, Chelsea and Westminster Hospital, London, and
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Dr M. R. Goodier, Department of Immunology, Imperial College London, Faculty of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
E-mail: m.goodier@ic.ac.uk

SUMMARY

Previous studies have shown that human natural killer (NK) cells are lost from the periphery and are functionally suppressed during HIV-1 infection, and that the administration of highly active antiretroviral therapy (HAART) results in a recovery of NK cell numbers in HIV-1-infected individuals. However, despite this recovery, interleukin (IL)-2 + IL-12-driven interferon (IFN)-γ production by NK cells has been shown to remain suppressed after HAART. Here we show that the innate immune factor IL-15 in combination with IL-12 is also unable to recover NK cell IFN-γ production in HAART-treated individuals. Furthermore, we also demonstrate an imbalance in the distribution of CD56loCD16hi and CD56hiCD16 NK subsets after successful HAART, CD56hiCD16 cells being reduced substantially in HIV-1 patients on HAART. Treatment of patients with combined human growth hormone and antiretroviral therapy resulted in further enhancement in the absolute numbers and the proportion of NK cells in some individuals in the absence of parallel effects on CD4+ T cells. Furthermore, in these individuals HAART with growth hormone resulted in an enhancement of cytokine-driven NK cell activation and IFN-γ production compared to the HAART-only baseline.

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