Depletion of OX-8 lymphocytes from the blood and airways using monoclonal antibodies enhances the late airway response in rats.

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Abstract

Recent evidence supports a role for T lymphocytes in allergic airway responses. We hypothesized that reducing blood T suppressor cells (Ts) might increase the late airway response (LR). Sprague-Dawley (SD) rats were sensitized with ovalbumin (OA). On days 8, 10, and 12, post-sensitization test SD (n = 14) received monoclonal antibody intravenously (OX-8; 1 mg) specific to rat Ts. Controls received saline (n = 7) or mouse ascites IgG (n = 7). On day 14, animals were challenged with OA aerosol (5% wt/vol) for 5 min, lung resistance was recorded for 8 h (n = 18) and bronchoalveolar lavage was performed. The LR was determined from the area under the lung resistance vs time curve from 75 to 480 min after challenge. In the remaining 10 rats, airway lymphocyte subsets were measured 8 h after OA aerosol challenge in minced and digested lungs. A decrease in percentage of blood and airway Ts, respectively, in test animals was observed vs controls (blood: 6.27 +/- 0.84 vs 32.95 +/- 1.94, P < 0.001); (airway: 5.05 +/- 0.66 vs 24.5 +/- 3.05, P < 0.02). Blood and airway helper T lymphocytes did not differ between test and control animals. The LR was significantly increased in test (22.89 +/- 3.92) vs controls (4.22 +/- 2.18, P < 0.001). Bronchoalveolar lavage macrophages, neutrophils and lymphocytes, and serum OA-specific IgE were also significantly elevated (P < 0.05) in test animals. We conclude that Ts play an important role in attenuating the LR in SD rats.

Authors

R Olivenstein, P M Renzi, J P Yang, P Rossi, S Laberge, S Waserman, J G Martin