Am. J. Respir. Crit. Care Med., Vol 151, No. 2, Feb 1995, 470-474.
Association between late allergic bronchoconstriction in the rat and allergen-stimulated lymphocyte proliferation in vitro
S Waserman, LJ Xu, R Olivenstein, PM Renzi and JG Martin
Respiratory Health Network of Centres of Excellence of Canada, Meakins- Christie Laboratories, McGill University, Montreal, Quebec.
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.
