A unique approach for the treatment of allergic disorders with new cytokine IGIF.

B细胞被认为是在用抗原和T辅助细胞刺激后产生IG的细胞。最近，我们发现IL-12和IL-18的组合诱导抗CD 40活化的B细胞产生IFN-γ，其抑制IL-4依赖性IgE的产生，这表明B细胞也可以作为调节细胞（PNAS，1997）。由于B细胞需要与IL-12共刺激以通过刺激IFN-γ的产生来响应IL-18，我们研究了IL-18 R的B细胞表达。我们发现IL-12刺激的B细胞表达高亲和力和低亲和力的IL-18 R。IL-18和IL-12的施用显著诱导T、B和NK细胞产生IFN-γ，其抑制体内IgE的产生（PNAS，1997）。因此，IL-12和IL-18决定了Th 1和Th 2的平衡，从而决定了免疫应答期间产生的IgE水平。我们还证明了来自SJL小鼠的T细胞耗尽（抗Thy-1/抗Lyt-1加C依赖性）的B细胞（已知其在蠕虫感染时产生IgE的遗传能力差）在体外用LPS和IL-4刺激后不能产生IgE，这是由于污染的巨噬细胞产生的IL-12和IL-18的作用。此外，我们证明了来自LPS刺激的巨噬细胞的IL-18和IL-12协同诱导独特的T细胞（CD 4-CD 8-双阴性CD 3 intIL-2 R β +T细胞）分泌IFN-γ并表达FasL，其组合抑制来自B细胞的IgE产生（J. Immunol. In Press）。因此，由巨噬细胞分泌的IL-12和IL-18可能在决定Th 1/Th 2应答的平衡以及因此决定IG产生中起关键作用。IL-12和IL-18的给药可以提供治疗过敏性疾病的独特方法。

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.