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

使用新细胞因子 IGIF 治疗过敏性疾病的独特方法。

基本信息

批准号：
08670542
负责人：
NAKANISHI Kenji
金额：
$ 1.47万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670542/
关键词：
B cells IFN-gamma IL-12 IL-18 IL-18R IgE SJL mice CD3intoIL-2Rbeta+T cells IFNγ SJL CD3^+IL-2Rβ^+IGIF Fas

项目摘要

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.

B细胞被认为是用抗原和T辅助细胞刺激后产生Ig的细胞。最近，我们表明IL-12和IL-18的组合诱导抗CD40激活的B细胞产生IFN-GAMMA，从而抑制IL-4依赖性IgE的产生，这表明B细胞也可以充当调节细胞（PNAS，1997）。由于B细胞需要与IL-12共同刺激通过打击IFN-gamma的产生来对IL-18响应IL-18，因此我们研究了IL-18R的B细胞表达。我们发现IL-12刺激的B细胞表达了高和低亲和力IL-18R.Admin.Administion.Administration.Administion IL-12和IL-12产生T，IFN和NK-nk细胞的时，IL-12刺激的B细胞表达了IL-18R。（PNAS，1997）。因此，IL-12和IL-18确定Th1和Th2的平衡，因此，在免疫反应过程中产生的IgE水平。我们还证明了SJL小鼠的T细胞耗尽（抗Thy-1/抗Lyt-1 Plus C依赖性C依赖性C依赖性）B细胞，这些B细胞以其在蠕虫感染时产生IgE的遗传能力而闻名，由于IL-12和IL-12的作用，在LPS和IL-4对Vitro的刺激后未能产生IgE，而IL-4则无法产生IL-4和IL-18的作用。此外，我们证明了来自LPS刺激的巨噬细胞中的IL-18和IL-12协同诱导独特的T细胞（CD4-CD8-double CD3INTIL-2RBETA+T细胞）分泌IFN-GAMMA并表达FASL，并表达FASL，以抑制B细胞的IGE生产（J.Mmunol。）。因此，巨噬细胞的IL-12和IL-18分泌可能在确定Th1/Th2响应的平衡以及Ig产生的平衡中起关键作用。 IL-12和IL-18的给药可以提出一种用于治疗过敏性疾病的独特方法。