Differential effects of pharmacologic agents on EAC3 rosette formation by lymphocytes from normal and asthmatic subjects.

We studied the effect of isoproterenol hydrochloride (I) and theophylline (Th) on EAC3 rosette formation by lymphocytes from 30 normal adult subjects, 35 asthmatic subjects, 11 subjects who were age and sex matched with the asthma group, and 10 subjects with allergic rhinitis. Baseline EAC3 rosette numbers were similar for all groups (normal adults, 13.2%; normal children, 15.1%; rhinitis, 14.4%; asthma, 14.6%). Incubation with I and Th in the presence of fetal calf serum caused enchancement of EAC3 rosette formation by lymphocytes from normal adults (mean increase, 52% with I and 53% with Th), from normal age- and sex-matched controls (mean increase, 45% with I and 40% with Th), from subjects with allergic rhinitis (mean increase, 50% with I and 52% with Th), but not by lymphocytes from asthmatic subjects (mean increase, 0% with I and 2% with Th). These results were not affected by bronchodilator therapy. Similar results were obtained with cholera toxin, prostaglandin E₁ and adrenaline, suggesting that the defect in lymphocytes from asthmatic patients resides at the level of 3′, 5′-cyclic adenosine monophosphate (cAMP) production or at the level of cAMP-triggered events. Lymphocyte fractionation experiments into T cell-rich, B cell-rich, and null cell populations revealed that the null cell population was a target for the I-mediated enhancement of EAC3 rosette formation. Null cells from normal subjects, but not from asthmatic subjects, exhibited an increase in the number of EAC3 rosettes formed following incubation with I. This enhancement required protein synthesis as it was prevented by the addition of puromycin hydrochloride. The resistance of peripheral blood lymphocytes from asthmatics to the enhancing effect of I and Th on EAC3 rosette formation may be used to study the biochemical defect in asthma and should be assessed for possible use in the detection of the latent asthmatic.