Choi Garam, Kim Byung-Seok, Park Young-Jun, Shim Inbo, Chung Yeonseok
Laboratory of Immune Regulation, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea.
BK21 Plus Program, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Immune Netw. 2017 Jun;17(3):163-170. doi: 10.4110/in.2017.17.3.163. Epub 2017 Jun 20.
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 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 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 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.
变应原特异性CD4 T细胞的扩增是过敏性哮喘诱导气道炎症过程中的关键步骤。T细胞的这种克隆性扩增是通过引流淋巴结中携带变应原的树突状细胞与变应原特异性初始T细胞之间的相互作用启动的。吸入变应原的主要器官——肺中是否也会发生这种T细胞克隆性扩增仍不清楚。与野生型小鼠相比，我们发现在反复暴露于吸入变应原后，淋巴结缺陷小鼠肺中CD4 T细胞的频率相似。此外，在用CFSE标记的OT-II T细胞进行的增殖研究中，我们观察到在用S1P拮抗剂FTY720处理的变应原激发小鼠的肺中，有明显一群CD4 T细胞发生了克隆性扩增。此外，与野生型小鼠相比，变应原特异性CD4 T细胞在小鼠肺中的扩增显著增强。这些结果共同表明，变应原特异性CD4 T细胞的克隆性扩增在没有淋巴结的情况下也会发生，这表明肺可以作为CD4 T细胞对吸入变应原作出反应进行克隆性扩增的主要部位。
