Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
J Immunol. 2010 Aug 15;185(4):2222-30. doi: 10.4049/jimmunol.1000024. Epub 2010 Jul 16.
A CD30 ligand (CD30L; CD153) and its receptor, CD30, is a membrane-associated glycoprotein belonging to the TNF superfamily and TNFR superfamily. These were expressed preferentially by activated CD4(+)T cells. In this paper, we show that CD44(low)CD62(hi)CD4(+) T cells from CD30L(-/-) or CD30(-/-) mice exhibited impaired differentiation into Th17 cells but an increased ability to produce IL-2 after in vitro culture under Th17-polarizing conditions. Neutralization with IL-2 by anti-IL-2 mAb partly restored the ability of Th17 differentiation in CD30L(-/-) or CD30(-/-) T cells. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed IL-2 production by CD30(-/-)CD4(+) T cells, indicating that the reverse signal to CD30L is responsible for downregulation of IL-2 production. In vivo Th17 differentiation of CD30L(-/-)CD4(+)CD45RB(high) T cells was also impaired after transfer into SCID mice, whereas CD30L(+/+)CD4(+)CD45RB(high) T cells normally differentiated into Th17 cells in CD30L(-/-) SCID mice. The results of these studies demonstrate that CD30L/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production.
CD30 配体（CD30L；CD153）及其受体 CD30 是一种膜相关糖蛋白，属于 TNF 超家族和 TNFR 超家族。这些蛋白主要表达在激活的 CD4+T 细胞上。在本文中，我们表明 CD30L（-/-）或 CD30（-/-）小鼠的 CD44（low）CD62（hi）CD4+T 细胞在体外 Th17 极化条件下培养时，向 Th17 细胞分化的能力受损，但产生 IL-2 的能力增加。用抗 IL-2 mAb 中和 IL-2 部分恢复了 CD30L（-/-）或 CD30（-/-）T 细胞中 Th17 分化的能力。通过固定化抗 CD30L mAb 刺激 CD30L 抑制了 CD30（-/-）CD4+T 细胞中 IL-2 的产生，表明 CD30L 的反向信号负责下调 IL-2 的产生。在体内，CD30L（-/-）CD4+CD45RB（high）T 细胞的 Th17 分化在转移到 SCID 小鼠后也受损，而 CD30L（+/+）CD4+CD45RB（high）T 细胞在 CD30L（-/-）SCID 小鼠中正常分化为 Th17 细胞。这些研究的结果表明，T-T 细胞相互作用执行的 CD30L/CD30 信号在 Th17 细胞分化中发挥关键作用，至少部分通过下调 IL-2 的产生。
