Interleukin 15 signal negatively regulates Dendritic Cell Activity in contact hypersensitivity

Abstract

Interleukin‐15 (IL‐15) plays important roles in the regulation of immune responses. In IL‐15 knockout (IL‐15−/−) mice, the activation and function of NK and CD8+ T cells are impaired whereas CD4+ T cells are less affected. Evidence indicates that dendritic cells (DC) is able to produce IL‐15 and that DC derived IL‐15 is required for the stimulation of NK and T cells. However, the effect of IL‐15 on DC cells is less clear. We show here that IL‐15−/− DC are more active than wild type DC in the activation of CD4+ T cells and induction of contact hypersensitivity responses (CHS). IL‐15−/− or IL‐15 receptor knockout (IL‐15R−/−) DC produced a lower level of IL‐12p70 and IFN‐g than wild type DC, as reported in previous studies. However, we found that they also produced a higher level of IL‐12 p40 and IL‐23 and a lower level of IL‐10 than wild type DC. Addition of exogenous recombinant IL‐15 in cultures reduced the production of IL‐12p40 and IL‐23 but increased IL‐12p70, IFN‐g and IL‐10 by IL‐15−/− but not IL‐15R−/− DC. Adoptive transfer of hapten labeled IL‐15−/− or IL‐15R−/− DC into naïve wild type mice induced a higher level of CHS than wild type DC. IL‐15−/− DC that were treated with IL‐15 induced a similar level of CHS as wild type DC. Similarly, IL‐15−/− DC stimulated higher levels of IFN‐g and IL‐17 production by hapten primed T cells and OT‐II cell proliferation in cultures than wild type DC. This effect was abrogated by pre‐treatment of IL‐15−/− DC with IL‐15. The data provide insights into a novel mechanism for IL‐15 mediated regulation of immune responses. It implicate that IL‐15 increases the production of immune suppressive cytokines IL‐10 and inhibits the function of DC in the stimulation of T cells and induction of immune responses.