Color-coded real-time cellular imaging of lung T-lymphocyte accumulation and focus formation in a mouse asthma model

Akihiro Hasegawa, Katsuhiro Hayashi, Hiroyuki Kishimoto, Meng Yang, Soichi Tofukuji, Kazuo Suzuki, Hiroshi Nakajima, Robert M. Hoffman, Mutsunori Shirai, Toshinori Nakayama

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: A critical role for CD4+TH2 cells in the pathogenesis of acute asthma has been demonstrated in the studies of human asthma as well as of animal models of asthma. TH2-cell migration into the lung is crucial for the initiation of asthma phenotype, but the dynamics of this process are poorly understood because it has been difficult to visualize this process. Objective: Our aim was to image the cellular dynamics of the migration of TH2 cells into the lung of living animals in a mouse model of asthma and identify the cellular processes required for the initiation of the asthma phenotype. Methods: We developed a color-coded real-time imaging model of cell migration into the lung using green fluorescent protein (GFP) and red fluorescent protein (RFP) transgenic CD4 T cells. Results: Selective accumulation of antigen-specific CD4 T cells in the lungs was quantitatively imaged in a mouse model of asthma. The inhibition of accumulation by dexamethasone was imaged. Accumulating GFP+ TH2 cells formed foci in the lungs from 6 to 20 hours after antigen inhalation. This process was also inhibited by the administration of anti-intercellular adhesion molecule 1 or anti-vascular cell adhesion molecule 1 mAbs. Two days after inhalation of antigen, GFP+ TH2 cells were detected in the area of eosinophil infiltration. Conclusion: Focus formation generated by accumulating antigen-specific TH2 cells in the lung appeared to be a critical process in the initiation of the asthma phenotype. This new model enables the study of in vivo cell biology of airway inflammation and novel drug discovery for lung inflammatory diseases.

Original languageEnglish
Pages (from-to)461-468.e6
JournalJournal of Allergy and Clinical Immunology
Volume125
Issue number2
DOIs
Publication statusPublished - Feb 2010

Keywords

  • GFP
  • ICAM-1
  • Real-time in vivo cellular imaging
  • T2 cells
  • VCAM-1
  • airway inflammation
  • cellular dynamics
  • focus formation
  • mouse model of asthma,

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Hasegawa, A., Hayashi, K., Kishimoto, H., Yang, M., Tofukuji, S., Suzuki, K., Nakajima, H., Hoffman, R. M., Shirai, M., & Nakayama, T. (2010). Color-coded real-time cellular imaging of lung T-lymphocyte accumulation and focus formation in a mouse asthma model. Journal of Allergy and Clinical Immunology, 125(2), 461-468.e6. https://doi.org/10.1016/j.jaci.2009.09.016