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

Abstract

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.

Cutting Edge: IL-10-Producing CD4+ T Cells Mediate Tumor Rejection

“…In fact, a number of recent studies demonstrate that IL-10 directly enhances NK cell, as well as CD8 ϩ T cell, cytotoxicity in vitro. NK cells pretreated with IL-10, either alone or in combination with other cytokines such as IL-2, IL-18, and IL-12, are more efficient at lysing YAC-1 cells and tumor targets (28,29). IL-10 might play a similar role in our model because GL261 gliomas are susceptible to lysis by activated NK cells ex vivo (data not shown).…”

Stat4-dependent, T-bet-independent regulation of IL-10 in NK cells

“…[7][8][9][10][11] In addition, IL-10 has been shown to enhance NK cell proliferation and/or production of IFN-g. [12][13][14] Various cell types can be divided into distinct subpopulations based on IL-10 expression patterns. In the myeloid compartment, alternatively activated macrophages, type II macrophages and some DC subsets are the principle sources of IL-10 production.…”

Regulation of T cells and cytokines by the interleukin‐10 (IL‐10)‐family cytokines IL‐19, IL‐20, IL‐22, IL‐24 andIL‐26

“…IL-10 inhibits monocyte/macrophage function during inflammation by down-regulating the production of proinflammatory cytokines, such as IL-12 and TNF-a, and suppressing the surface expression of major histocompatibility class II [3,4]. It has been shown to activate B cells for immunoglobulin production, induce proliferation of mast cells and increase NK cell cytotoxicity [5][6][7]. IL-10 can also inhibit CD4 + T cell chemotaxis towards IL-8 [1,8] and T cell apoptosis [9] by leading to Bcl-2 up-regulation.…”