Color-coded real-time cellular imaging of lung T-lymphocyte accumulation and focus formation in a mouse asthma model.
BACKGROUND
A critical role for CD4(+)T(H)2 cells in the pathogenesis of acute asthma has been demonstrated in the studies of human asthma as well as of animal models of asthma. T(H)2-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 T(H)2 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(+) T(H)2 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(+) T(H)2 cells were detected in the area of eosinophil infiltration.


CONCLUSIONS
Focus formation generated by accumulating antigen-specific T(H)2 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.
Hasegawa
Akihiro
A
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Hayashi
Katsuhiro
K
Kishimoto
Hiroyuki
H
Yang
Meng
M
Tofukuji
Soichi
S
Suzuki
Kazuo
K
Nakajima
Hiroshi
H
Hoffman
Robert M
RM
Shirai
Mutsunori
M
Nakayama
Toshinori
T
D000818:Animals; D001249:Asthma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008164:Luminescent Proteins; D008168:Lung / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D000097573:Red Fluorescent Protein
D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein