Human NK cell IFN-gamma production is regulated by endogenous TGF-beta.
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.
Meadows
Sarah K
SK
Department of Microbiology and Immunology, Dartmouth Medical School, 6W Borwell Bldg, One Medical Center Drive, Lebanon, NH 03756, USA.
Eriksson
Mikael
M
Barber
Amorette
A
Sentman
Charles L
CL
D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D019002:CD56 Antigen / Q000032:analysis; D004149:Dioxoles / Q000494:pharmacology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011070:Poly I-C / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists; D051196:Toll-Like Receptor 3 / Q000819:agonists; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015054:Zymosan / Q000494:pharmacology
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D000911:Antibodies, Monoclonal; D001549:Benzamides; D019002:CD56 Antigen; D004149:Dioxoles; D019409:Interleukin-15; D047428:Protein Kinase Inhibitors; D018125:Receptors, Transforming Growth Factor beta; C495342:TLR2 protein, human; C495344:TLR3 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D007371:Interferon-gamma; D015054:Zymosan; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D011070:Poly I-C