Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells
Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells
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DOI：
10.1073/pnas.94.8.3948
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
Nakanishi, K
中科院分区：
文献类型：
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作者：
Yoshimoto, T;Okamura, H;Nakanishi, K
白细胞介素18（IL-18）是新近克隆的由枯否细胞和活化的巨噬细胞合成的约18 kDa的细胞因子，最初称为干扰素（IFN）-γ诱导因子。与该分子相关的主要活性是在IL-12存在的情况下诱导抗CD 3激活的辅助性T细胞1产生IFN-γ。当用抗-CD 40和IL-4刺激时，B细胞产生IgG 1和IgE。在这里，我们表明，IL-12和IL-18的组合诱导抗CD 40激活的B细胞产生IFN-γ，其抑制IL-4依赖性IgE和IgG 1的产生，并增强IgG 2a的产生，而不抑制B细胞增殖反应。我们还显示，24.3%的B细胞在用IL-12和IL-18刺激后变得胞质IFN-γ阳性。此外，我们发现，与用抗CD 3、IL-12和IL-18刺激的脾T细胞一样，B细胞响应于抗CD 40、IL-12和IL-18产生高水平的IFN-γ。将IL-12和IL-18的混合物注射到接种有巴西日本圆线虫或注射有抗IgD的小鼠中诱导IFN-γ产生细胞，其抑制它们中的IgE产生。此外，从正常小鼠获得的B细胞可以在IFN-γ（-/-）宿主小鼠中响应于用IL-12和IL-18的体内处理而发育成IFN-γ产生细胞。这些结果表明，来自活化的B细胞的IFN-γ在体外和体内不同地调节IgG 1/IgE和IgG 2a应答，表明B细胞在免疫应答中充当调节细胞。目前的研究结果表明，注射IL-12和IL-18可能是治疗过敏性疾病的独特方法。
Interleukin 18 (IL-18), originally called interferon (IFN)-gamma-inducing factor, is a recently cloned cytokine of approximately 18 kDa synthesized by Kupffer cells and activated macrophages. The major activity associated with this molecule is the induction of IFN-gamma production from anti-CD3-activated T helper 1 cells in the presence of IL-12. B cells produce IgG1 and IgE when stimulated with anti-CD40 and IL-4. Here we show that a combination of IL-12 and IL-18 induces anti-CD40-activated B cells to produce IFN-gamma, which inhibits IL-4-dependent IgE and IgG1 production and enhances IgG2a production without inhibiting the B cell proliferative response. We also show that 24.3% of B cells became positive for cytoplasmic IFN-gamma after being stimulated with IL-12 and IL-18. Furthermore, we show that, like splenic T cells stimulated with anti-CD3, IL-12, and IL-18, B cells produced high level of IFN-gamma in response to anti-CD40, IL-12, and IL-18. Injection of a mixture of IL-12 and IL-18 into mice inoculated with Nippostrongylus brasiliensis or injected with anti-IgD induced IFN-gamma-producing cells that inhibit IgE production in them. Furthermore, B cells obtained from normal mice could develop into IFN-gamma-producing cells in IFN-gamma(-/-) host mice in response to in vivo treatment with IL-12 and IL-18. These results indicate that IFN-gamma from activated B cells differentially regulates IgG1/IgE and 1gG2a responses in vitro and in vivo, indicating that B cells act as regulatory cells in the immune response. Present results suggested that injection of IL-12 and IL-18 could present a unique approach for the treatment of allergic disorders.