title: Blomia tropicalis-Specific TCR Transgenic Th2 Cells Induce Inducible BALT and Severe Asthma in Mice by an IL-4/IL-13-Dependent Mechanism.
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.
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Yen Leong
authors.identifier: 0000-0002-6025-0496
authors.initials: YL
authors.lastname: Chua
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Ka Hang
authors.identifier: 0000-0002-7575-032X
authors.initials: KH
authors.lastname: Liong
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228, Singapore.
authors.forename: Chiung-Hui
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Hok Sum
authors.initials: HS
authors.lastname: Wong
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Say Siong
authors.identifier: 0000-0002-7202-4453
authors.initials: SS
authors.lastname: Ler
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Chin Pei
authors.initials: CP
authors.lastname: Low
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Hui Yu
authors.identifier: 0000-0003-1031-1630
authors.initials: HY
authors.lastname: Koh
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228, Singapore.
authors.forename: I-Chun
authors.identifier: 0000-0002-2472-1510
authors.initials: IC
authors.lastname: Kuo
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Yongliang
authors.identifier: 0000-0002-4964-1285
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 117597, Singapore; and.
authors.forename: W S Fred
authors.initials: WS
authors.lastname: Wong
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 117597, Singapore; and.
authors.forename: Hong Yong
authors.initials: HY
authors.lastname: Peh
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Hwee Ying
authors.initials: HY
authors.lastname: Lim
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Translational Lung Biology Center, Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, CA 95616.
authors.forename: Moyar Qing
authors.identifier: 0000-0002-5407-342X
authors.initials: MQ
authors.lastname: Ge
authors.affiliation: Translational Lung Biology Center, Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, CA 95616.
authors.forename: Angela
authors.identifier: 0000-0002-1301-4941
authors.initials: A
authors.lastname: Haczku
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Veronique
authors.identifier: 0000-0002-2759-3497
authors.initials: V
authors.lastname: Angeli
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: Paul A
authors.identifier: 0000-0002-1139-8996
authors.initials: PA
authors.lastname: MacAry
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore.|Department of Paediatrics, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228, Singapore.
authors.forename: Kaw Yan
authors.initials: KY
authors.lastname: Chua
authors.affiliation: Immunology Programme, Center for Life Sciences, National University of Singapore, Singapore 117456, Singapore; mickdm@nus.edu.sg.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 1117545, Singapore.
authors.forename: David M
authors.identifier: 0000-0001-7964-6151
authors.initials: DM
authors.lastname: Kemeny
mesh_terms: D040041:Acaridae / Q000276:immunology*; D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D007073:Immunoglobulin E; D018793:Interleukin-13 / Q000008:administration & dosage / Q000276:immunology*; D015847:Interleukin-4 / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011657:Pulmonary Eosinophilia / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D018793:Interleukin-13; D011948:Receptors, Antigen, T-Cell; C094701:allergen Blo t 5; D015847:Interleukin-4; D007073:Immunoglobulin E