IL‐10 enhances NK cell proliferation, cytotoxicity and production of IFN‐γ when combined with IL‐18

G Cai, RA Kastelein, CA Hunter - European journal of …, 1999 - Wiley Online Library
European journal of immunology, 1999Wiley Online Library
Previous studies have shown that IL‐10 inhibits the accessory cell functions required for
production of IFN‐γ by T cells and NK cells. Our results show that although IL‐10 did not
induce the production of IFN‐γ by NK cells, it did enhance the ability of IL‐18 to stimulate NK
cell production of IFN‐γ. 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‐γ or proliferate, but there was an additive effect with IL‐12 …
Abstract
Previous studies have shown that IL‐10 inhibits the accessory cell functions required for production of IFN‐γ by T cells and NK cells. Our results show that although IL‐10 did not induce the production of IFN‐γ by NK cells, it did enhance the ability of IL‐18 to stimulate NK cell production of IFN‐γ. 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‐γ 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‐γ and NK cell cytotoxicity. The ability of IL‐10 to elevate the production of IFN‐γ appeared to be specific for NK cells since IL‐10 had no effect on the production of IFN‐γ 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 α and β 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.
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