The expansion of allergen-specific CD4+ T cells is a critical step in inducing airway inflammation during allergic asthma. Such clonal expansion of T cells is initiated through the interaction between allergen-bearing dendritic cells and allergen-specific naïve T cells in the draining lymph nodes. Whether such T cell clonal expansion also occurs in the lung, the primary organ encountering inhaled allergens, remains unclear. Compared with wild-type mice, we found similar frequencies of CD4+ T cells in the lung of lymph node-deficient Rorgtgfp/gfp mice after repeated exposure to inhaled allergens. In addition, we observed an evident population of CD4+ T cells that underwent clonal expansion in the lung of allergen-challenged mice treated with an S1P antagonist FTY720 in an in vivo proliferation study with CFSE-labeled OT-II T cells. Moreover, the expansion of allergen-specific CD4+ T cells was significantly enhanced in the lungs of Rorgtgfp/gfp mice in comparison to that of wild-type mice. These results together demonstrate that the clonal expansion of allergen-specific CD4+ T cells occurs in the absence of the lymph nodes, indicating that the lung can act as a primary site of the clonal expansion of CD4+ T cells in response to inhaled allergens.

中文翻译：

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无淋巴结时肺中过敏原特异性 CD4+ T 细胞的克隆扩增

过敏原特异性 CD4+ T 细胞的扩增是过敏性哮喘期间诱导气道炎症的关键步骤。T 细胞的这种克隆扩增是通过引流淋巴结中带有过敏原的树突细胞和过敏原特异性初始 T 细胞之间的相互作用而启动的。这种 T 细胞克隆扩增是否也发生在肺中，肺是遇到吸入过敏原的主要器官，目前尚不清楚。与野生型小鼠相比，我们发现在反复接触吸入过敏原后，淋巴结缺陷 Rorgtgfp/gfp 小鼠肺中 CD4+ T 细胞的频率相似。此外，在用 CFSE 标记的 OT-II T 细胞进行的体内增殖研究中，我们观察到明显的 CD4+ T 细胞群在用 S1P 拮抗剂 FTY720 治疗的过敏原攻击小鼠的肺中进行了克隆扩增。而且，与野生型小鼠相比，Rorgtgfp/gfp 小鼠肺中过敏原特异性 CD4+ T 细胞的扩增显着增强。这些结果共同证明，过敏原特异性 CD4+ T 细胞的克隆扩增发生在没有淋巴结的情况下，表明肺可以作为 CD4+ T 细胞克隆扩增的主要部位，以响应吸入的过敏原。