Dynamics of antigen-specific helper T cells at the initiation of airway eosinophilic inflammation.
Bronchial asthma is characterized by chronic eosinophilic inflammation of the bronchial mucosa in which Th2 cells play crucial roles. Ovalbumin-reactive Th2 clones were labeled with a fluorescent-probe then infused into unprimed mice to elucidate the dynamics of antigen-specific T cells involved in allergic inflammation. Infiltration of not only labeled antigen-specific T cells, but also unlabeled nonspecific CD4(+) T cells into the bronchial mucosa following inhaled antigen challenge was detectable under confocal microscopy and flow cytometry. Accordingly, labeled T cells in the spleen were decreased, whereas those in hilar lymph nodes were increased upon antigen challenge. Approximately 45% of antigen-specific T cells that migrated into the lungs bore CD25, while another early activation marker, CD69, was expressed on 80% of the migrated T cells. Accordingly, antigen challenge to the mice induced in situ proliferation of antigen-specific T cells as well as bronchial epithelial cells in the lungs. Expression of vascular cell adhesion molecule (VCAM)-1, but not intercellular adhesion molecule (ICAM)-1, on the vascular endothelium in the lungs was enhanced following antigen challenge. Nevertheless, treatment with anti-VCAM-1 antibody, and also anti-ICAM-1 antibody strongly suppressed the accumulation of T cells, suggesting that both VCAM-1 and ICAM-1 are essential for antigen-stimulated T cell mobilization into peripheral tissues. Our current study visualized the kinetics and the mechanism of antigen-specific T cell migration in response to local challenge with a protein antigen.
Kaminuma
O
O
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan. kaminuma@rinshoken.or.jp
Fujimura
H
H
Fushimi
K
K
Nakata
A
A
Sakai
A
A
Chishima
S
S
Ogawa
K
K
Kikuchi
M
M
Kikkawa
H
H
Akiyama
K
K
Mori
A
A
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology*; D002465:Cell Movement; D002999:Clone Cells; D007249:Inflammation / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007700:Kinetics; D008168:Lung / Q000276:immunology / Q000648:ultrastructure; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000648:ultrastructure; D018418:Th2 Cells / Q000276:immunology* / Q000637:transplantation; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D010047:Ovalbumin