To evaluate the role of lymphocytes in the pathogenesis of allergic bronchoconstriction, we investigated whether allergic airway responses are adoptively transferred by antigen-primed lymphocytes in Brown Norway (BN) rats. Animals were actively sensitized to ovalbumin (OA) or sham sensitized, and 14 d later mononuclear cells (MNCs) were isolated from intrathoracic lymph nodes, passed through a nylon wool column, and transferred to naive syngeneic rats. Recipients were challenged with aerosolized OA or bovine serum albumin (BSA) (5% wt/vol) and analyzed for changes in lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), and bronchoalveolar lavage (BAL) cells. Recipients of MNCs from sensitized rats responded to OA inhalation and exhibited sustained increases in RL throughout the 8-h observation period, but without usual early airway responses. Recipients of sham-sensitized MNCs or BSA-challenged recipients failed to respond to antigen challenge. At 32 h after OA exposure, airway responsiveness to MCh was increased in four of seven rats that had received sensitized MNCs (p = 0.035). BAL eosinophils increased at 32 h in the recipients of both sensitized and sham-sensitized MNCs. However, eosinophil numbers in BAL were inversely correlated with airway responsiveness in the recipients of sensitized MNCs (r = -0.788, p = 0.036). OA-specific immunoglobulin E (IgE) was undetectable by enzyme-linked immunosorbent assay (ELISA) or passive cutaneous anaphylaxis (PCA) in recipient rats following adoptive transfer. In conclusion, allergic late airway responses (LAR) and cholinergic airway hyperresponsiveness, but not antigen-specific IgE and early responses, were adoptively transferred by antigen-primed lymphocytes in BN rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Airway hyperresponsiveness to inhalational challenge with methacholine (MCh) develops by 32 h after allergen challenge of actively sensitized BN rats. To test the hypothesis that CD4+ T cells mediate allergen-induced hyperresponsiveness independent of IgE-mediated mechanisms, we administered CD4+ T cells, CD8+ T cells, and a mixture of CD4+ and CD8+ T cells (total T cells) isolated from the cervical lymph nodes of rats sensitized with ovalbumin (OA) to naive BN rats that underwent aerosol challenge with either OA or bovine serum albumin (BSA) 2 d later. Responsiveness to MCh was measured 2 d before transfer of T cells and 32 h after challenge with OA or BSA. Airway responsiveness increased significantly in recipients of CD4+ T cells after OA challenge, but not in any other of the treatment groups. Analysis of bronchoalveolar lavage (BAL) cells for major basic protein expression by immunostaining showed eosinophilia in OA-challenged CD4+ and total T-cell recipients. Cells retrieved by bronchoalveolar lavage showed increased expression of IL-5 mRNA (in situ hybridization) in CD4+ T cell recipients after OA challenge compared with other groups. Interferon-gamma mRNA was expressed to the greatest extent in CD8+ recipients, but it was elevated in both OA- and BSA-challenged animals. We conclude that CD4+ T cells can induce airway hyperresponsiveness after inhalational challenge with allergen and this is associated with IL-5 production and eosinophilia. CD8+ T cells may have a negative regulatory effect on responsiveness, possibly mediated by interferon-gamma.