Depletion of CD8+ T cells enhances airway remodelling in a rodent model of asthma.
Airway remodelling is induced by persistent airway inflammation and may lead to severe asthma. T cells play a pivotal role in asthmatic airway inflammation but their role in remodelling is poorly understood. Although previous studies have revealed that CD8(+) T cells inhibit the late airway response and airway inflammation in a rat model of asthma, their effects on airway remodelling have not been evaluated. The aim of this study was to examine the role of CD8(+) T cells in airway remodelling. Brown Norway rats were sensitized with ovalbumin (OVA) on day 0. CD8(+) T cells in rats were depleted during the repeated challenges by treating them with a CD8alpha monoclonal antibody (OX-8). Control rats were treated with mouse ascites. Sensitized rats were challenged with OVA on days 14, 19 and 24 or were sham challenged with phosphate-buffered saline. On day 29, bronchoalveolar lavage and lung tissues were harvested. Repeated OVA inhalations evoked significant increases in the numbers of periodic acid-Schiff-positive epithelial cells and proliferating cell nuclear antigen-positive epithelial cells, and in airway smooth muscle mass compared to the control group. CD8-depleted rats had significant enhancement of these changes, principally affecting the large airways. These results suggest that endogenous CD8(+) T cells have inhibitory effects on airway remodelling in this model of asthma.
Department of Integrated Pulmonology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Kimitake
K
Tsuchiya
Susumu
S
Isogai
Meiyo
M
Tamaoka
Naohiko
N
Inase
Takumi
T
Akashi
James G
JG
Martin
Yasuyuki
Y
Yoshizawa
D000485:Allergens / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D004847:Epithelial Cells / Q000473:pathology; D015870:Gene Expression / Q000276:immunology; D020397:Goblet Cells / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D009093:Mucus / Q000378:metabolism; D009130:Muscle, Smooth / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D020545:Respiratory Mucosa / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000485:Allergens; D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; C431698:CD8alpha antigen; D016207:Cytokines; D012333:RNA, Messenger; D010047:Ovalbumin; D004247:DNA