Induced bronchus-associated lymphoid tissue serves as a general priming site for T cells and is maintained by dendritic cells.

Induced bronchus-associated lymphoid tissue serves as a general priming site for T cells and is maintained by dendritic cells.
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DOI:
10.1084/jem.20091472
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发表时间:
2009-11-23
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Förster R
Förster R
中科院分区:
其他
文献类型:
--
作者:
Halle S;Dujardin HC;Bakocevic N;Fleige H;Danzer H;Willenzon S;Suezer Y;Hämmerling G;Garbi N;Sutter G;Worbs T;Förster R

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通过呼吸道接种黏多糖可以在动物感染模型中引起保护性免疫,但其潜在机制仍知之甚少。我们表明,一个单一的鼻内应用程序的复制缺陷型修饰的牛痘病毒安卡拉,这是广泛使用的重组疫苗接种载体,结果在显着的诱导支气管相关淋巴组织(BALT)。虽然最初的细支气管周围浸润,其特征在于树突状细胞(DC)和少量淋巴细胞的存在下,可以发现病毒应用后4天,有组织的淋巴样结构与分离的B和T细胞区是在第8天首次观察到。双光子显微镜观察发现,在体外分化的抗原负载的DC可迅速迁移到预先形成的BALT中,并有效激活抗原特异性T细胞。此外,在表达白喉毒素受体的CD11c启动子控制下的小鼠中,肺特异性消耗DC干扰BALT维持。总的来说,这些数据将BALT鉴定为三级淋巴结构,其支持针对不相关的空气传播抗原的T细胞应答的有效引发,同时关键地需要DC用于其持续存在。
Mucosal vaccination via the respiratory tract can elicit protective immunity in animal infection models, but the underlying mechanisms are still poorly understood. We show that a single intranasal application of the replication-deficient modified vaccinia virus Ankara, which is widely used as a recombinant vaccination vector, results in prominent induction of bronchus-associated lymphoid tissue (BALT). Although initial peribronchiolar infiltrations, characterized by the presence of dendritic cells (DCs) and few lymphocytes, can be found 4 d after virus application, organized lymphoid structures with segregated B and T cell zones are first observed at day 8. After intratracheal application, in vitro–differentiated, antigen-loaded DCs rapidly migrate into preformed BALT and efficiently activate antigen-specific T cells, as revealed by two-photon microscopy. Furthermore, the lung-specific depletion of DCs in mice that express the diphtheria toxin receptor under the control of the CD11c promoter interferes with BALT maintenance. Collectively, these data identify BALT as tertiary lymphoid structures supporting the efficient priming of T cell responses directed against unrelated airborne antigens while crucially requiring DCs for its sustained presence.
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