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


METHODS
The effects of IL-21 on perforin expression, proliferation, degranulation, interferon (IFN)-gamma 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-gamma, 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 CD56 cells in chronically HIV-infected individuals was diminished. Perforin expression in CD56 and CD56 was comparable in healthy and HIV-infected individuals. IL-15 upregulated perforin expression primarily in CD56 NK cells, whereas IL-21 upregulated perforin in both NK subsets. IL-21 and IL-15 upregulated CD107a and IFN-gamma, 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.


CONCLUSIONS
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.
Strbo
Natasa
N
Center for HIV Research, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
de Armas
Lesley
L
Liu
Huanliang
H
Kolber
Michael A
MA
Lichtenheld
Mathias
M
Pahwa
Savita
S
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D002908:Chronic Disease; D003601:Cytotoxicity Tests, Immunologic; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology; D007378:Interleukins / Q000276:immunology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000032:analysis; D008875:Middle Aged; D054353:Perforin / Q000032:analysis / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000032:analysis / Q000378:metabolism; D000098546:Interleukin-21
D015415:Biomarkers; D019002:CD56 Antigen; D019409:Interleukin-15; D007378:Interleukins; D052118:Lysosomal-Associated Membrane Protein 1; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D054353:Perforin; D007371:Interferon-gamma; D000098546:Interleukin-21