Blomia tropicalis-Specific TCR Transgenic Th2 Cells Induce Inducible BALT and Severe Asthma in Mice by an IL-4/IL-13-Dependent Mechanism.
Blomia tropicalis-Specific TCR Transgenic Th2 Cells Induce Inducible BALT and Severe Asthma in Mice by an IL-4/IL-13-Dependent Mechanism.
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DOI：
10.4049/jimmunol.1502676
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发表时间：
2016-11-15
期刊：
影响因子：
--
通讯作者：
Kemeny DM
中科院分区：
文献类型：
--
作者：
Chua YL;Liong KH;Huang CH;Wong HS;Zhou Q;Ler SS;Tang Y;Low CP;Koh HY;Kuo IC;Zhang Y;Wong WS;Peh HY;Lim HY;Ge MQ;Haczku A;Angeli V;MacAry PA;Chua KY;Kemeny DM
以往的研究强调了肺引流淋巴结在呼吸道过敏免疫反应中的重要性，而肺实质免疫系统在很大程度上被忽视了。我们描述了一种新的呼吸致敏的体内模型，该模型对热带地区主要的哮喘过敏原Blomia tropicalis进行了研究，在该模型中，免疫反应通过一种新型TCR转基因小鼠的Th2细胞转移，集中在肺组织上，特异性针对主要的热带b.s tropicalis过敏原Blo t 5，其目标是肺而不是引流淋巴结。转移高度极化的转基因CD4效应Th2细胞，称为BT-II，然后反复吸入Blo t 5，使这些细胞在肺中扩增100倍，随后的Blo t 5刺激导致体温下降、运动减少和特定肺顺应性下降，这在常规小鼠哮喘模型中是不可见的，在生理过敏原刺激后。这些小鼠表现出肺嗜酸性粒细胞增多；平滑肌细胞、胶原蛋白、杯状细胞增生；高IgE综合征；粘液堵塞;广泛诱导型BALT。此外，在100ms时，总肺活量和用力呼气量下降。通过在第1,2,3周给予IL-4和IL-13特异性的中和单克隆抗体，这些病理生理变化大大减少，在某些情况下完全消除。这种依赖IL-4/ il -13的诱导型BALT模型将有助于研究哮喘的病理生理机制和开发治疗严重哮喘的更有效药物。
Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes. Transfer of highly polarized transgenic CD4 effector Th2 cells, termed BT-II, followed by repeated inhalation of Blo t 5 expands these cells in the lung >100-fold, and subsequent Blo t 5 challenge induced decreased body temperature, reduction in movement, and a fall in specific lung compliance unseen in conventional mouse asthma models following a physiological allergen challenge. These mice exhibit lung eosinophilia; smooth muscle cell, collagen, and goblet cell hyperplasia; hyper IgE syndrome; mucus plugging; and extensive inducible BALT. In addition, there is a fall in total lung volume and forced expiratory volume at 100 ms. These pathophysiological changes were substantially reduced and, in some cases, completely abolished by administration of neutralizing mAbs specific for IL-4 and IL-13 on weeks 1, 2, and 3. This IL-4/IL-13–dependent inducible BALT model will be useful for investigating the pathophysiological mechanisms that underlie asthma and the development of more effective drugs for treating severe asthma.
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影响因子：
15.3
作者：
Croft, Michael;Carter, Laura;Swain, Susan L.;Dutton, Richard W.
通讯作者：
Dutton, Richard W.
影响因子：
14.2
作者：
Kuo, IC;Cheong, N;Chua, KY
通讯作者：
Chua, KY
DOI：
10.1164/rccm.200308-1094oc
发表时间：
2004-02-01
影响因子：
24.7
作者：
Johnson, JR;Wiley, RE;Jordana, M
通讯作者：
Jordana, M
影响因子：
14.2
作者：
ARLIAN, LG;VYSZENSKIMOHER, DL;FERNANDEZCALDAS, E
通讯作者：
FERNANDEZCALDAS, E
DOI：
10.1016/j.bbrc.2004.02.148
发表时间：
2004-04-16
影响因子：
3.1
作者：
Lim, LH;Li, HY;Chua, KY
通讯作者：
Chua, KY