Adoptive transfer of allergen‐specific CD4+ T cells induces airway inflammation and hyperresponsiveness in Brown–Norway rats

Abstract

Following allergen exposure, sensitized Brown–Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25⁺) in the airways. We tested the hypothesis that CD4⁺ T cells are involved directly in the acquisition of AHR. Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH)₃, showed a dose-dependent proliferative response in vitro to ovalbumin, but not to bovine serum albumin, as measured by []> ³H]thymidine uptake. For total T-cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by a nylon wool column separation. CD4⁺ and CD8⁺ T cells were purified by immunomagnetic beads cell separation. Recipient naive rats were injected intravenously with 50×10⁶ total T cells, 20×10⁶ and 5×10⁶ CD4⁺cells, and 5×10⁶ CD8⁺ cells, and were exposed to ovalbumin aerosol 24 hr afterwards. After a further 24 hr, airway responsiveness to acetylcholine (ACh) was measured and provocative concentration (PC) values (PC₁₀₀, PC₂₀₀ andPC₃₀₀) (the ACh concentration needed to achieve 100, 200 and 300% increase in lung resistance above baseline) were calculated. Airway responsiveness was significantly increased in recipients of sensitized total T cells compared with recipients of cells from saline-injected donor rats (P+ cell counts/mm² in airway submucosal tissue in the hyperreactive rats and a significant correlation was found between the number of MBP⁺ cells and PC₁₀₀ (r = 0·75; P+ T cells from sensitized donors induced AHR in naive recipients (P+ and naive CD4⁺ cells failed to do so. Our data indicate that T cells may induce AHR through an eosinophilic airway inflammation and that CD4⁺ T cells may have a direct effect in this process in Brown–Norway rats.