Pötzl Johann, Botteron Catherine, Tausch Eugen, Pedré Xiomara, Mueller André M, Männel Daniela N, Lechner Anja
Institute of Immunology, University of Regensburg, Regensburg, Germany.
PLoS One. 2008 Aug 13;3(8):e2951. doi: 10.1371/journal.pone.0002951.
The function of T helper cell subsets in vivo depends on their location, and one hallmark of T cell differentiation is the sequential regulation of migration-inducing chemokine receptor expression. CC-chemokine receptor 6 (CCR6) is a trait of tissue-homing effector T cells and has recently been described as a receptor on T helper type 17 (Th17) cells. Th17 cells are associated with autoimmunity and the defence against certain infections. Although, the polarization of Th cells into Th17 cells has been studied extensively in vitro, the development of those cells during the physiological immune response is still elusive.
METHODOLOGY/PRINCIPAL FINDINGS: We analysed the development and functionality of Th17 cells in immune-competent mice during an ongoing immune response. In naïve and vaccinated animals CCR6(+) Th cells produce IL-17. The robust homeostatic proliferation and the presence of activation markers on CCR6(+) Th cells indicate their activated status. Vaccination induces antigen-specific CCR6(+) Th17 cells that respond to in vitro re-stimulation with cytokine production and proliferation. Furthermore, depletion of CCR6(+) Th cells from donor leukocytes prevents recipients from severe disease in experimental autoimmune encephalomyelitis, a model for multiple sclerosis in mice.
CONCLUSIONS/SIGNIFICANCE: In conclusion, we defined CCR6 as a specific marker for functional antigen-specific Th17 cells during the immune response. Since IL-17 production reaches the highest levels during the immediate early phase of the immune response and the activation of Th17 cells precedes the Th1 cell differentiation we tent to speculate that this particular Th cell subset may represent a first line effector Th cell subpopulation. Interference with the activation of this Th cell subtype provides an interesting strategy to prevent autoimmunity as well as to establish protective immunity against infections.
体内辅助性T细胞亚群的功能取决于其所处位置，而T细胞分化的一个标志是对迁移诱导趋化因子受体表达的顺序调控。CC趋化因子受体6（CCR6）是组织归巢效应T细胞的一个特征，最近被描述为辅助性T17（Th17）细胞上的一种受体。Th17细胞与自身免疫及针对某些感染的防御有关。尽管在体外对Th细胞向Th17细胞的极化进行了广泛研究，但这些细胞在生理性免疫反应过程中的发育仍不清楚。
方法/主要发现：我们分析了免疫活性小鼠在持续免疫反应过程中Th17细胞的发育和功能。在未免疫和已接种疫苗的动物中，CCR6(+) Th细胞产生白细胞介素-17（IL-17）。CCR6(+) Th细胞强大的稳态增殖及激活标志物的存在表明它们处于激活状态。接种疫苗可诱导抗原特异性CCR6(+) Th17细胞，这些细胞在体外再次受到刺激时会通过产生细胞因子和增殖做出反应。此外，从供体白细胞中去除CCR6(+) Th细胞可使受体在实验性自身免疫性脑脊髓炎（一种小鼠多发性硬化模型）中免于患重病。
结论/意义：总之，我们将CCR6定义为免疫反应过程中功能性抗原特异性Th17细胞的一种特异性标志物。由于在免疫反应的即刻早期阶段IL-17的产生达到最高水平，且Th17细胞的激活先于Th1细胞分化，我们推测这个特定的Th细胞亚群可能代表一线效应Th细胞亚群。干扰这一Th细胞亚型的激活为预防自身免疫以及建立针对感染的保护性免疫提供了一种有趣的策略。
