Molecular immunological analysis for IgE production and a unique NK cell population producing type 2 cytokine, IL-13

IgE 产生和产生 2 型细胞因子 IL-13 的独特 NK 细胞群的分子免疫学分析

• 批准号: 11670468
• 负责人: HOSHINO Tomoaki
• 金额: $ 2.18万
• 依托单位: KURUME UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670468/
• 关键词: Cytokines; Transgenic mouse; Allergy; Th1; Th2; IL-4; IL-13; NK細胞

IL-18 has been shown to be a strong co-factor for Th1 T cell development. However, we previously demonstrated that when IL-18 was combined with IL-2, there was a synergistic induction of a Th2 cytokine, IL-13, in both T and NK cells (T.Hoshino, J.Immunol. 162 : 5070, 1999). More recently, we and other groups have reported IL-18 can potentially induce IgE, IgG1 and Th2 cytokine production in murine experimental models (T.Hoshino, Eur. J.Immunol. 30 : 1998, 2000).Here we report on the generation of IL-18 transgenic (Tg) mice in which mouse mature IL-18 cDNA fused to the signal peptide of the mouse Ig κ-chain was expressed. CD8^+ CD44^<high> T cells and macrophages were increased, but B cells were decreased in these mice while serum IgE, IgG1, IL-4 and IFN-γ levels were significantly increased. Splenic T cells in IL-18 Tg mice produced higher levels of IFN-γ, IL-4, IL-5 and IL-13 than control wild type mice. Thus, aberrant expression of IL-18 in vivo results in the increased production of both Th1 and Th2 cytokines.

IL-18已被证明是Th 1 T细胞发育的强辅助因子。然而，我们先前证明，当IL-18与IL-2组合时，在T和NK细胞中存在Th 2细胞因子IL-13的协同诱导（T.Hoshino，J. Immunol.162：5070，1999）。最近，我们和其他小组已经报道IL-18可以在鼠实验模型中潜在地诱导IgE、IgG 1和Th 2细胞因子产生（T.Hoshino，Eur.免疫学杂志30：1998，2000）。在此，我们报道了IL-18转基因（Tg）小鼠的产生，其中表达了与小鼠IG κ链的信号肽融合的小鼠成熟IL-18 cDNA。CD 8 ^+ CD 44 ^<high>T细胞和巨噬细胞增加，B细胞减少，血清IgE、IgG 1、IL-4和IFN-γ水平显著升高。IL-18 Tg小鼠中的脾T细胞产生比对照野生型小鼠更高水平的IFN-γ、IL-4、IL-5和IL-13。因此，体内IL-18的异常表达导致Th 1和Th 2细胞因子的产生增加。

项目成果

Hoshino T, Winkler-Pickett RT, Mason AT, Ortaldo JR, Young HA: "IL-13 production by NK cells : IL-13 producing NK and T cells are present in vivo in the absence of IFN-γ."J.Immunol.. 162. 51-59 (1999)

Hoshino T、Winkler-Pickett RT、Mason AT、Ortaldo JR、Young HA：“NK 细胞产生 IL-13：在缺乏 IFN-γ 的情况下，产生 IL-13 的 NK 和 T 细胞存在于体内。”J.Immunol .. 162. 51-59 (1999)

Hoshino T,et al.: "IL-13 production by NK cells"J.Immunology. 162. 51-59 (1999)

Hoshino T 等人：“NK 细胞产生 IL-13”J.Immunology。

Kim SH, Reznikov LL, Stuyt RJ, Selzman CH, Fantuzzi G, Hoshino T, Young HA, Dinarello CA: "Functional reconstitution and regulation of IL-18 activity by IL-18Rβ chain."J.Immunol.. 166. 148-154 (2001)

Kim SH、Reznikov LL、Stuyt RJ、Selzman CH、Fantuzzi G、Hoshino T、Young HA、Dinarello CA：“IL-18Rβ 链对 IL-18 活性的功能重建和调节。”J.Immunol.. 166. 148- 154（2001）

Hoshino T: "In vivi administration of IL-18 can induce IgE production through Th2 cytokine induction and up-regulation of CD40 ligand (CD154) expression on CD4+ T cells."Eur.J.Immunol.. 30. 1998-2006 (2000)

Hoshino T：“体内施用 IL-18 可以通过 Th2 细胞因子诱导和 CD4 T 细胞上 CD40 配体 (CD154) 表达的上调来诱导 IgE 产生。”Eur.J.Immunol.. 30. 1998-2006 (2000

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