Non-T cell-derived IL-4 plays an important role in IgE production induced by antigen resensitization and is resistant to FK506

The present study investigates the role of non-T cell-derived IL-4 in IgE production. It is well known that IL-4 is generally produced by T cells and induces IgE production. We have demonstrated that non-T cells also produce IL-4 in vivo by injection with Ag following passive sensitization of mice with IgE. In contrast to its known potent immunosuppressive effects on T cells, FK506 only partially inhibited IL-4 produced by non-T cells; therefore, FK506 was found to be a useful tool for identifying a cell source of IL-4 production. We used this observation to examine the role of non-T cell-derived IL-4 in IgE production. The production of a high titer of IgE was induced by priming BALB/c mice with Ascaris suum extract and further enhanced by secondary immunization. The IgE production in this model was dependent on IL-4, since both primary and secondary IgE production were completely suppressed by injection with anti-IL-4 Ab. Although primary IgE production was completely inhibited by FK506, secondary IgE production was not inhibited. Furthermore, IL-4 induction in plasma was only partially inhibited by FK506 when the A. suum extract-primed mice were resensitized with Ag. These results indicate that IL-4 produced by non-T cells plays a crucial role in secondary IgE production.