Abstract
NK cells are an important component of innate immunity, and they can promote CTL and Th1 cell development and macrophage activation via cytokines. TGF-beta is believed to be an important immunoregulatory molecule, and for this reason several TGF-beta inhibitors are currently in clinical development. However, the modulation of specific innate immune responses by endogenous human TGF-beta remains unclear. In this study, we demonstrate that blocking the action of endogenous TGF-beta resulted in an increase in both the percentage of responding NK cells and the amount of IFN-gamma produced by human NK cells when stimulated by monokines and TLR agonists. Blocking endogenous TGF-beta resulted in significant NK cell IFN-gamma production under suboptimal stimulation conditions. Our findings also suggest that TGF-beta associated with other blood cells may be involved in limiting NK cell activation. Thus, inhibiting endogenous TGF-beta provides a means to shift NK cell activation and promote cellular immunity.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Activin Receptors, Type I / antagonists & inhibitors
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Antibodies, Monoclonal / pharmacology
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Benzamides / pharmacology
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CD56 Antigen / analysis
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Dioxoles / pharmacology
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Female
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Humans
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Interferon-gamma / biosynthesis*
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Interferon-gamma / metabolism
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Interleukin-12 / pharmacology
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Interleukin-15 / pharmacology
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Killer Cells, Natural / chemistry
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / metabolism*
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / metabolism
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Male
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Poly I-C / pharmacology
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Protein Kinase Inhibitors / pharmacology
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type I
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Receptors, Transforming Growth Factor beta / antagonists & inhibitors
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism
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Toll-Like Receptor 2 / agonists
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Toll-Like Receptor 3 / agonists
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Transforming Growth Factor beta / immunology
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Transforming Growth Factor beta / metabolism
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Transforming Growth Factor beta / physiology*
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Zymosan / pharmacology
Substances
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4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
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Antibodies, Monoclonal
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Benzamides
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CD56 Antigen
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Dioxoles
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Interleukin-15
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Protein Kinase Inhibitors
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Receptors, Transforming Growth Factor beta
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TLR2 protein, human
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TLR3 protein, human
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Toll-Like Receptor 2
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Toll-Like Receptor 3
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Transforming Growth Factor beta
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Interleukin-12
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Interferon-gamma
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Zymosan
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Protein Serine-Threonine Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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Poly I-C