A Novel Function of Vα14+CD4+NKT Cells: Stimulation of IL-12 Production by Antigen-Presenting Cells in the Innate Immune System
A Novel Function of Vα14+CD4+NKT Cells: Stimulation of IL-12 Production by Antigen-Presenting Cells in the Innate Immune System
复制标题
DOI：
10.4049/jimmunol.163.1.93
复制
发表时间：
1999-07
期刊：
影响因子：
--
通讯作者：
M. Tomura;Wen-gong Yu;H. Ahn;M. Yamashita;Yi-fu Yang;S. Ono;T. Hamaoka;T. Kawano;M. Taniguchi;Y. Koezuka;H. Fujiwara
中科院分区：
文献类型：
--
作者：
M. Tomura;Wen-gong Yu;H. Ahn;M. Yamashita;Yi-fu Yang;S. Ono;T. Hamaoka;T. Kawano;M. Taniguchi;Y. Koezuka;H. Fujiwara
Th1 和 Th2 发育之间的平衡由 IL-4 和 IL-12 决定。虽然 CD4+ NK1.1+ T (NKT) 细胞在影响这种平衡中的作用已根据其产生 IL-4 的能力得到认可，但尚不清楚它们参与的先天免疫系统中如何产生 IL-12。这项研究表明，Ag 激活的 CD4+ NKT 细胞表达 CD40 配体 (CD40L) (CD154)，该配体与 APC 上的 CD40 结合并刺激它们产生 IL-12。使用能够选择性刺激 Vα14/Jα281+ NKT 细胞的 α-半乳糖苷神经酰胺 (α-GalCer) 培养 C57BL/6 小鼠的 B 细胞耗尽的脾细胞，导致产生 IL-12 以及 IFN-γ 和 IL-4。 α-GalCer 诱导的 IL-12 产生发生在 I-Abβ 缺陷型小鼠中，但在 β2-微球蛋白缺陷型和 Vα14/Jα281 TCR 缺陷型小鼠中则不然，并且被抗 CD40L mAb 抑制。在 CD4+ 和 CD4− NKT 细胞中，CD4+ NKT 亚群优先表现出在 α-GalCer 刺激后表达 CD40L/CD154 并触发 IL-12 产生的能力。在 α-GalCer 处理的小鼠中也观察到 IL-12 的产生。 IL-12 的产生先于 IFN-γ 的产生，并且 IFN-γ 的产生需要 IL-12，但不需要 IL-4。 IL-12 和 IL-4 的产生之间存在刺激/抑制关系。这些结果说明了 CD4+ NKT 细胞的一种新功能，可能参与 Th1 与 Th2 发育的调节。
The balance between Th1 and Th2 development is determined by IL-4 and IL-12. While the role for CD4+ NK1.1+ T (NKT) cells in influencing this balance has been recognized based on their capacity to produce IL-4, it is unknown how IL-12 is produced in the innate immune system in which they participate. This study demonstrates that Ag-activated CD4+ NKT cells express CD40 ligand (CD40L) (CD154), which engages CD40 on APC and stimulates them to produce IL-12. Culture of B cell-depleted spleen cells from C57BL/6 mice with α-galactosylceramide (α-GalCer) capable of selectively stimulating Vα14/Jα281+ NKT cells resulted in the production of IL-12 together with IFN-γ and IL-4. α-GalCer-induced IL-12 production occurred in I-Abβ-deficient mice, but not in β2-microglobulin-deficient and Vα14/Jα281 TCR-deficient mice, and was inhibited by anti-CD40L mAb. Of CD4+ and CD4− NKT cells, the capacity to express CD40L/CD154 and trigger IL-12 production following α-GalCer stimulation was exhibited preferentially by the CD4+ NKT subset. IL-12 production was also observed in α-GalCer-treated mice. Production of IL-12 preceded IFN-γ production, and IL-12 was required for IFN-γ, but not IL-4, production. A stimulatory/inhibitory relationship existed between IL-12 and IL-4 production. These results illustrate a novel function of CD4+ NKT cells that could be involved in the regulation of Th1 vs Th2 development.