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IL-21 augments natural killer effector functions in chronically HIV-infected individuals

Strbo, Natasaa,b; de Armas, Lesleya,b; Liu, Huanlianga,b; Kolber, Michael Ac; Lichtenheld, Mathiasa,b; Pahwa, Savitaa,b

doi: 10.1097/QAD.0b013e3283089367
Basic Science

Objective: This study addresses the interleukin (IL)-21 effects on resting peripheral blood natural killer (NK) cells in chronically HIV-infected individuals.

Design: The effects of IL-21 on perforin expression, proliferation, degranulation, interferon (IFN)-γ production, cytotoxicity and induction of STAT phosphorylation in NK cells were determined in vitro.

Methods: Peripheral blood mononuclear cells from HIV-infected and healthy individuals were incubated in vitro for 6 h, 24 h or 5 days with IL-21 or IL-15. Percentages of perforin, IFN-γ, CD107a, NKG2D and STAT3–5 positive cells were determined within NK cell populations. K562 cells were used as target cells in NK cytotoxicity assay.

Results: Frequency of CD56dim cells in chronically HIV-infected individuals was diminished. Perforin expression in CD56dim and CD56bright was comparable in healthy and HIV-infected individuals. IL-15 upregulated perforin expression primarily in CD56bright NK cells, whereas IL-21 upregulated perforin in both NK subsets. IL-21 and IL-15 upregulated CD107a and IFN-γ, as well as NK cytotoxicity. IL-15 predominantly activated STAT5, whereas IL-21 activated STAT5 and STAT3. IL-15, but not IL-21 increased NK cell proliferation in uninfected and HIV-infected individuals.

Conclusion: IL-21 augments NK effector functions in chronically HIV-infected individuals and due to its perforin enhancing properties it has potential for immunotherapy or as a vaccine adjuvant.

aCenter for HIV Research, USA

bDepartment of Microbiology and Immunology, USA

cDepartment of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.

Received 14 June, 2007

Revised 1 May, 2008

Accepted 13 May, 2008

Correspondence to Savita Pahwa, MD, Department of Microbiology and Immunology, 1580 NW 10th Avenue, BCRI 712, Miami, FL 33136, USA. Tel: +1 305 243 7732; fax: +1 305 243 7211; e-mail: spahwa@med.miami.edu

© 2008 Lippincott Williams & Wilkins, Inc.