CD30 Ligand/CD30 Plays a Critical Role in Th17 Differentiation in Mice
CD30 Ligand/CD30 Plays a Critical Role in Th17 Differentiation in Mice
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DOI：
10.4049/jimmunol.1000024
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发表时间：
2010-08-15
影响因子：
4.4
通讯作者：
Yoshikai, Yasunobu
中科院分区：
文献类型：
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作者：
Sun, Xun;Yamada, Hisakata;Yoshikai, Yasunobu
CD 30配体（CD 30 L; CD 153）及其受体CD 30是属于TNF超家族和TNFR超家族的膜相关糖蛋白。这些优先由活化的CD 4（+）T细胞表达。在这篇论文中，我们发现来自CD 30 L（-/-）或CD 30（-/-）小鼠的CD 44（低）CD 62（高）CD 4（+）T细胞在体外培养后在Th 17极化条件下表现出向Th 17细胞分化的受损，但产生IL-2的能力增加。抗IL-2 mAb中和IL-2后，部分恢复了CD 30 L（-/-）或CD 30（-/-）T细胞的Th 17分化能力。固定化抗CD 30 L mAb通过CD 30 L的刺激抑制了CD 30（-/-）CD 4（+）T细胞的IL-2产生，表明CD 30 L的反向信号是导致IL-2产生下调的原因。在体内，CD 30 L（-/-）CD 4（+）CD 45 RB（高）T细胞的Th 17分化在转移到SCID小鼠后也受损，而CD 30 L（+/+）CD 4（+）CD 45 RB（高）T细胞在CD 30 L（-/-）SCID小鼠中正常分化为Th 17细胞。这些研究的结果表明，由T-T细胞相互作用执行的CD 30 L/CD 30信号传导在Th 17细胞分化中起关键作用，至少部分地通过下调IL-2产生。免疫学杂志，2010，185：2222-2230。
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 down-regulation 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. The Journal of Immunology, 2010, 185: 2222-2230.