|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1997 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1996 : ¥1,100,000 (Direct Cost : ¥1,100,000)
B cells have been recognized as cells that produce Ig after being stimulated with antigen and T helper cells. Recently, we showed that a combination of IL-12 and IL-18 induce anti-CD40-activated B cells to produce IFN-gamma, which inhibits IL-4-dependent IgE production, suggesting that B cells can also act as a regulatory cells (PNAS,1997) . As B cells require co-stimulation with IL-12 to respond to IL-18 by striking IFN-gamma production, we investigated B cell expression of IL-18R.We found IL-12-stimulated B cells express both high and low affinity IL-18R.Administration of IL-18 and IL-12 strikingly induces T,B and NK cells to produce IFN-gamma that inhibits IgE production in vivo (PNAS,1997) . Thus, IL-12 and IL-18 determines the balance of Th1 and Th2, therefore, the levels of IgE produced during an immune response. We also demonstrated that T cell-depleted (anti-Thy-1/anti-Lyt-1 plus C-dependent) B cells from SJL mice, which are known for their genetically poor ability to produce IgE upon helminth infection, fails to produce IgE following stimulation with LPS and IL-4 in vitro, due to the actions of IL-12 and IL-18 produced by contaminating macrophages. Furthermore, we demonstrated that IL-18 and IL-12 from LPS-stimulated macrophages synergistically induce unique T cells (CD4-CD8-double negative CD3intIL-2Rbeta+T cells) to secrete IFN-gamma and to express FasL,which in combination inhibits IgE production from B cells (J.Immunol. In Press) . Thus, IL-12 and IL-18 secretion by macrophages may play a crucial role in determining the balance of Th1/Th2 responses, and hence, Ig production. Administration of IL-12 and IL-18 could present a unique approach for the treatment of allergic disorders.