1] Department of Immunology, China Medical University, Shenyang, China [2] Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan [3] Research Center for Advanced Immunology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mucosal Immunol. 2013 Nov;6(6):1191-201. doi: 10.1038/mi.2013.18. Epub 2013 Apr 3.
CD30 ligand (CD30L, CD153), a member of the tumor necrosis factor (TNF) superfamily, and its receptor CD30 are important for differentiation and activation of CD4(+) T helper type 17 (Th17) cells. In this report, we demonstrate that the interleukin 17A (IL-17A)-producing γδ T cells normally developed in the fetal thymus, whereas Vγ1(-)Vγ4(-) γδ T cells expressed Vγ6/Vδ1 gene transcript selectively decreased in mucosa-associated tissues in naive CD30KO or CD30LKO mice. Moreover, CD30 and CD30L were expressed preferentially by Vγ1(-)Vγ4(-) γδ T cells in naive mice. The bacteria clearance was attenuated by the impaired response of the IL-17A-producing γδ T cells and decreased infiltration of neutrophils in CD30KO or CD30LKO mice. In vivo administration of agonistic anti-CD30 monoclonal antibody restored the ability of protection against Listeria monocytogenes by enhancing Vγ1(-)Vγ4(-) γδ T cells producing IL-17A not only in wild-type but also CD30LKO mice. Taken together, it appears that CD30L/CD30 signaling plays an important role in the maintenance and activation of IL-17A-producing γδ T cells presumably bearing Vγ6 in the mucosa-associated tissues of mice.
CD30 配体（CD30L，CD153）是肿瘤坏死因子（TNF）超家族的成员，其受体 CD30 对于 CD4+辅助性 T 细胞 17（Th17）细胞的分化和激活很重要。在本报告中，我们证明了在胎儿胸腺中正常发育的白细胞介素 17A（IL-17A）产生的 γδ T 细胞，而在幼稚 CD30KO 或 CD30LKO 小鼠的黏膜相关组织中，Vγ1(-)Vγ4(-)γδ T 细胞选择性地表达减少Vγ6/Vδ1 基因转录。此外，CD30 和 CD30L 在幼稚小鼠中优先表达于 Vγ1(-)Vγ4(-)γδ T 细胞。IL-17A 产生的 γδ T 细胞反应受损和中性粒细胞浸润减少，导致细菌清除能力减弱。在体内给予激动性抗 CD30 单克隆抗体，通过增强产生 IL-17A 的 Vγ1(-)Vγ4(-)γδ T 细胞，不仅在野生型小鼠，而且在 CD30LKO 小鼠中恢复了对李斯特菌的保护能力。总之，CD30L/CD30 信号似乎在维持和激活可能在小鼠黏膜相关组织中携带 Vγ6 的 IL-17A 产生的 γδ T 细胞中发挥重要作用。
