Effect of CD8+ T-cell depletion on bronchial hyper-responsiveness and inflammation in sensitized and allergen-exposed Brown-Norway rats.
We examined the role of CD8+ T cells in a Brown-Norway rat model of asthma, using a monoclonal antibody to deplete CD8+ T cells. Ovalbumin (OA)-sensitized animals were given anti-CD8 antibody (0.5 mg/rat) intravenously 1 week prior to exposure to 1% OA aerosol and were studied 18-24 hr after aerosol exposure. Following administration of anti-CD8 antibody, CD8+ cells were reduced to <1% of total lymphocytes in whole blood and in spleen. In sensitized animals, OA exposure induced bronchial hyper-responsiveness (BHR), accumulation of eosinophils, lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid, and also an increase in tissue eosinophils and CD2+, CD4+ and CD8+ T cells in airways. Anti-CD8 antibody caused a further increase in allergen-induced BHR (P<0.03, compared with sham-treated animals), together with a significant increase in eosinophil number in BAL fluid (P<0.05). While CD2+ and CD4+ T cells in airways were not affected by anti-CD8 treatment, the level of CD8+ T cells was significantly reduced in sensitized, saline-exposed animals (P<0.04, compared with sham-treated rats), and sensitized and OA-challenged rats (P<0.002, compared with sham-treated rats). Using reverse transcription-polymerase chain reaction, an increase of T helper (Th)2 cytokine [interleukin (IL)-4 and IL-5], and also of Th1 cytokine [interferon-gamma (IFN-gamma) and IL-2], mRNA in the lung of sensitized and OA-exposed animals was found; after CD8+ T-cell depletion, Th1 cytokine expression was significantly reduced (P<0.02), while Th2 cytokine expression was unchanged. CD8+ T cells have a protective role in allergen-induced BHR and eosinophilic inflammation, probably through activation of the Th1 cytokine response.
Huang
T J
TJ
Thoracic Medicine, Chang Gung Memorial Hospital, Keelung Branch, Taiwan, China; Thoracic Medicine, National Heart & Lung Institute, Imperial College School of Medicine, London, UK.
MacAry
P A
PA
Kemeny
D M
DM
Chung
K F
KF
D000109:Acetylcholine / Q000276:immunology; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D015139:Blotting, Southern; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D007124:Immunoenzyme Techniques; D008168:Lung / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014665:Vasodilator Agents / Q000276:immunology
D000485:Allergens; D000911:Antibodies, Monoclonal; D016207:Cytokines; D014665:Vasodilator Agents; D010047:Ovalbumin; D000109:Acetylcholine