IL-10 enhances NK cell proliferation, cytotoxicity and production of IFN-gamma when combined with IL-18.
Previous studies have shown that IL-10 inhibits the accessory cell functions required for production of IFN-gamma by T cells and NK cells. Our results show that although IL-10 did not induce the production of IFN-gamma by NK cells, it did enhance the ability of IL-18 to stimulate NK cell production of IFN-gamma. In addition, IL-10 augmented NK cell proliferation and cytotoxic activity when combined with IL-18. However, IL-10 did not affect the ability of IL-12 to stimulate NK cells to produce IFN-gamma or proliferate, but there was an additive effect with IL-12 to increase NK cell cytotoxic activity. Interestingly, the type I IFN, whose receptors (R) are related to the IL-10R, also enhanced the effects of IL-18 on NK cell production of IFN-gamma and NK cell cytotoxicity. The ability of IL-10 to elevate the production of IFN-gamma appeared to be specific for NK cells since IL-10 had no effect on the production of IFN-gamma by Th1 clones stimulated with IL-18 or IL-12 in the presence of a monoclonal antibody specific for CD3. These latter results correlated with lower mRNA levels for the alpha and beta chains of the IL-10R in Th1 cells than observed in NK cells. Thus, the ability of IL-10 and IL-18 to up-regulate NK cell function, but not Th1 cell activity, appears to be based on expression of the IL-10R.
Cai
G
G
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104-6008, USA.
Kastelein
R A
RA
Hunter
C A
CA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004357:Drug Synergism; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000494:pharmacology*; D020382:Interleukin-18 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D020382:Interleukin-18; D016753:Interleukin-10; D007371:Interferon-gamma