Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis
Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis
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自身免疫性脑脊髓炎免疫治疗过程中可溶性抗原对外周免疫器官效应T细胞的即时作用
DOI：
10.1073/pnas.0608383104
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
A. Flügel
中科院分区：
文献类型：
--
作者：
F. Odoardi;N. Kawakami;Zhaoxia Li;C. Cordiglieri;K. Streyl;M. Nosov;W. Klinkert;J. Ellwart;J. Bauer;H. Lassmann;H. Wekerle;A. Flügel
静脉内输注天然自身抗原或其改变的肽变体是治疗自身免疫性疾病的重要治疗选择，因为它选择性地靶向疾病诱导T细胞。为了更多地了解这种方法的机制和动力学，我们使用活体动物脾脏的实时视频和双光子原位成像，可视化了静脉输注肽或完整蛋白对GFP标记的自身攻击性CD4+效应T细胞的关键初始作用。我们发现，静脉注射完整的蛋白质到T细胞行为的第一次变化之间的时间间隔非常短;在蛋白质应用后10分钟内，T细胞的运动性发生了急剧变化。它们的生长速度变慢，并与局部的无柄基质细胞相连。部分细胞聚集成簇。在随后的20分钟内，IFN-γ mRNA大量上调（> 100倍）;表面IL-2受体和OX-40（CD 134）在1.5小时后增加。这些过程耗尽血液循环中的自身免疫T细胞，将细胞捕获在外周淋巴器官中，从而防止它们侵入CNS。这种特异性阻断几乎完全消除了CNS炎症和临床疾病。这些发现突出了体内抗原识别的速度和效率，并增加了我们对T细胞介导的自身免疫的理解。
i.v. infusion of native autoantigen or its altered peptide variants is an important therapeutic option for the treatment of autoimmune diseases, because it selectively targets the disease-inducing T cells. To learn more about the mechanisms and kinetics of this approach, we visualized the crucial initial effects of i.v. infusion of peptides or intact protein on GFP-tagged autoaggressive CD4+ effector T cells using live-video and two-photon in situ imaging of spleens in living animals. We found that the time interval between i.v. injection of intact protein to first changes in T cell behavior was extremely short; within 10 min after protein application, the motility of the T cells changed drastically. They slowed down and became tethered to local sessile stromal cells. A part of the cells aggregated to form clusters. Within the following 20 min, IFN-γ mRNA was massively (>100-fold) up-regulated; surface IL-2 receptor and OX-40 (CD 134) increased 1.5 h later. These processes depleted autoimmune T cells in the blood circulation, trapping the cells in the peripheral lymphoid organs and thus preventing them from invading the CNS. This specific blockage almost completely abrogated CNS inflammation and clinical disease. These findings highlight the speed and efficiency of antigen recognition in vivo and add to our understanding of T cell-mediated autoimmunity.
影响因子：
32.4
作者：
Negulescu, PA;Krasieva, TB;Cahalan, MD
通讯作者：
Cahalan, MD