Depletion of CD8+ T cells enhances pulmonary inflammation but not airway responsiveness after antigen challenge in rats.
BACKGROUND
CD8+ (OX-8+) T cells may suppress airway inflammation and airway responsiveness after allergen challenge.


OBJECTIVE
We studied the effects of depletion of OX-8+ T cells on allergen-induced lung eosinophilia and airway responsiveness in the Sprague-Dawley rat.


METHODS
Sprague-Dawley rats were sensitized to ovalbumin and challenged by aerosol 14 days later. Test animals received either low-dose (2 mg, n = 9) or high-dose (3 mg, n = 7) OX-8 monoclonal antibody (mAb), whereas controls (n = 8) received BALB/c ascites fluid. A fourth group of animals (n = 10) was not sensitized to ovalbumin and also received ascites fluid. Twenty-four hours after ovalbumin challenge, responsiveness to methacholine was measured, and lung inflammation was assessed in the large airways and small airways and parenchyma.


RESULTS
Circulating and airway CD8+ T cells were decreased by OX-8 mAb administration with greatest changes in animals treated with high-dose OX-8 mAb compared with controls (blood: 1.0% +/- 3.6% vs 18.7% +/- 3.9%, p < 0.05); (large airways: 2.5% +/- 1.2% vs 13.8% +/- 1.2%, p < 0.05). Ovalbumin challenge resulted in increases in macrophages and neutrophils in the small airways and parenchyma of sensitized compared with unsensitized rats (p < 0.05). High-dose OX-8 mAb further increased total leukocytes, attributable to increases in neutrophils and eosinophils, retrieved from the large airways and small airways and parenchyma compared with other groups (p < 0.05). Airway responsiveness to methacholine was not significantly different between control and ovalbumin-challenged animals and was not augmented by OX-8 pretreatment.


CONCLUSIONS
CD8+ T cells modulate the extent of allergen-induced airway inflammation. However, the enhancement of inflammation was not sufficient to affect airway responsiveness.
Laberge
S
S
Meakins-Christie Laboratories, Royal Victoria Hospital, Montreal, Quebec, Canada.
Wu
L
L
Olivenstein
R
R
Xu
L J
LJ
Renzi
P M
PM
Martin
J G
JG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000918:Antibody Specificity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007073:Immunoglobulin E / Q000032:analysis; D007249:Inflammation; D007428:Intradermal Tests; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D010047:Ovalbumin / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D007073:Immunoglobulin E; D010047:Ovalbumin