期刊
AIDS
卷 28, 期 9, 页码 1273-1278出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000000286
关键词
AIDS; CD57; HIV-1; immune activation; natural killer cells; NKG2A; subtype D
资金
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]
- U.S. Department of Defense
- National Institute of Allergy and Infectious Diseases (NIAID) [R01 AI34826, R01 AI34265]
- National Institute of Child and Health Development [5P30HD06826]
- Fogarty Foundation [5D43TW00010]
- Swedish Research Council
- Swedish Cancer Society
- Stockholm County Council
- Karolinska Institutet
- Division of Intramural Research, NIAID, NIH
Objective:Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse prognosis. HIV-1 infection causes perturbations to natural killer (NK) cells, and yet these cells can exert immune pressure on the virus and influence clinical outcome. Here, we studied NK cell activation and function in Ugandans with chronic untreated HIV-1 subtype D infection in comparison to uninfected community matched controls.Methods:Cryopreserved peripheral blood mononuclear cells (PBMCs) from 42 HIV-infected individuals and 28 HIV-negative controls were analysed using eight-colour flow cytometry. NK cell surface expression of CD16, CD56, CD57, HLA-DR and NKG2A were used to investigate activation, maturation and differentiation status. NK cell function was evaluated by measuring interferon-gamma (IFN) production in response to K562 cells, or interleukin (IL)-12 and IL-18.Results:CD56(dim) NK cells from HIV-infected individuals produced less IFN in response to IL-12 and IL-18 than did CD56(dim) NK cells from uninfected controls. Infected individuals had lower levels of CD56(dim) NK cells coexpressing the differentiation markers NKG2A and CD57 than controls. In addition, their NKG2A(+)CD57(+) CD56(dim) NK cells displayed elevated activation levels as assessed by HLA-DR expression. Cytokine-induced IFN production correlated directly with coexpression of CD57 and NKG2A on CD56(dim) NK cells.Conclusion:HIV-1 subtype D infection is associated with impaired NK cell responsiveness to cytokines, decline of the NKG2A(+)CD57(+) CD56(dim) NK cell subset, as well as elevated activation in this subset. These alterations within the NK cell compartment may contribute to immunopathogenesis of HIV-1 subtype D infection in Ugandans.
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