Blomia tropicalis-specific TCR transgenic Th2 cells induce inducible BALT and severe asthma in mice by an IL-4/IL-13-dependent mechanism

Yen Leong Chua, Ka Hang Liong, Chiung Hui Huang, Hok Sum Wong, Qian Zhou, Say Siong Ler, Yafang Tang, Chin Pei Low, Hui Yu Koh, I. Chun Kuo, Yongliang Zhang, W. S Fred Wong, Hong Yong Peh, Hwee Ying Lim, Moyar Qing Ge, Angela Franciska Haczku, Veronique Angeli, Paul A. MacAry, Kaw Yan Chua, David M. Kemeny

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3771-3781
Number of pages11
JournalJournal of Immunology
Volume197
Issue number10
DOIs
StatePublished - Nov 15 2016

ASJC Scopus subject areas

  • Immunology

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