Association between late allergic bronchoconstriction in the rat and allergen-stimulated lymphocyte proliferation in vitro.

Abstract

T lymphocytes are potentially of importance in determining the inflammatory response in the airways after allergen challenge. We hypothesized that the proliferative response of lymphocytes on exposure to allergen in vitro would be associated with the magnitude of the airway response in vivo after inhalational challenge. We studied Brown Norway rats that were actively sensitized with ovalbumin (OA) in aluminum hydroxide gel using Bordetella pertussis as an adjuvant. Two weeks later, blood mononuclear cells were isolated, and their proliferative response to culture with OA was measured with 3H-thymidine incorporation. Subsequently, the animals were anesthetized and challenged with aerosolized OA. Early allergic response (ER) and late (LR) allergic response were determined from the changes in pulmonary resistance (RL). Both significant ER and LR were observed in sensitized and challenged animals. The LR (measured as the area under the curve of RL against time) had a median value of 15.2 and ranged from 0.1 to 81.1 units. Lymphocyte proliferation occurred on exposure to OA (34,336 +/- 7,447 cpm) but less than after the mitogen Concanavalin A (250,685 +/- 76,676 cpm). The stimulation index (OA-stimulated 3H-thymidine incorporation standardized for baseline incorporation) was positively correlated with the magnitude of the late response. Interleukin-2 was significantly increased in the supernatant of cultured mononuclear cells exposed to OA, confirming T-cell activation. We conclude that the capacity of sensitized peripheral blood lymphocytes to respond to allergens may determine the magnitude of late airway responses.