Depletion of CD8 + T cells enhances pulmonary inflammation but not airway responsiveness after antigen challenge in rats

Abstract

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. CONCLUSION: CD8 + T cells modulate the extent of allergen-induced airway inflammation. However, the enhancement of inflammation was not sufficient to affect airway responsiveness. (J A LLERGY C LIN I MMUNOL 1996;98:617-27.)