Analysis of IgE production in vivo by CD1-specific CD4+NK 1.1+T cells and IGIF.

我们已经提出，小鼠CD-1特异性CD 4 +NK1.1+T细胞在体内刺激后迅速产生IL-4，对于诱导IL-4产生细胞和转换为IgE（IL-4依赖性事件）至关重要。我们进一步表明痤疮丙酸杆菌处理减少了CD 4 +NK1.1+T细胞，但通过诱导库普弗细胞产生IL-12和IL-18而诱导肝脏中的1型T细胞（J.Immunol.1997）。最近，我们发现IL-12和IL-18的组合诱导抗CD 40激活的B细胞产生IFNg，其抑制IL-4依赖性IgE的产生，这表明B细胞可以作为调节细胞（PNAS，1997）。由于B细胞需要用IL-12共刺激以通过打击IFNg产生来产生IL-18，我们研究了B细胞上的IL-18受体（IL-18 R）表达。我们还证明，SJL小鼠的T细胞耗尽的B细胞，已知其在寄生虫感染时产生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 3 intIL-2 R β +T细胞）分泌IFNg并表达Fas配体，其组合抑制来自B细胞的IgE产生（J.Immunol.出版中）。因此，IL-12和IL-18的给药可以提供治疗过敏性疾病的独特方法。

We have presented that mouse CD-1-specific CD4+NK1.1+T cells that produce IL-4 promptly upon in vivo stimulation, are essential for the induction of IL-4-producing cells and for switching to IgE,an IL-4-dependent event. We further showed that Propionibacterium acnes treatment diminishes CD4+NK1.1+T cells but induces type 1 T cells in the liver by induction of IL-12 and IL-18 production from kupffer cells (J.Immunol. 1997). These CD4+NK1.1+T cells diminished mice produced low levels of IgE.Recently, we showed that a combination of IL-12 and IL-18 induce anti-CD40-activated B cells to produce IFNg, which inhibits IL-4-dependent IgE production, suggesting that B cells can act as regulatory cells (PNAS,1997). As B cells require co-stimulation with IL-12 to produce IL-18 by striking IFNg production, we investigated IL-18 receptor (IL-18R) expression on B cells. We also demonstrated that T cell-depleted 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 action 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 (CD3intIL-2Rbeta+T cells) to secrete IFNg and to express Fas ligand, which in combination inhibits IgE production from B cells (J.Immunol. in press ). Thus administration of IL-12 and IL-18 could present a unique approach for the treatment of allergic disorders.