Heterogeneity of human lymphocyte subpopulations to pharmacologic stimulation : I. Lymphocyte responsiveness to beta adrenergic agents

Measurement of lymphocyte cyclic 3′5′-adenosine monophosphate (cyclic AMP) has been used in man to study the potential beta adrenergic defect in asthma. In this study, we evaluated the possibility of heterogeneity of beta adrenergic response with the use of the E rosette technique for thymic-derived (T) lymphocytes to compare a rosette-forming cell (RFC)-rich T cell population with a RFC-depleted (predominately bursal derived B lymphocyte) population. Lymphocytes were isolated and categorized into 4 populations: whole (unseparated) lymphocytes, RFC-rich, and RFC-depleted populations and a recombination population consisting of E-rosetting cells (T lymphocytes) + immunofluorescent-staining cells (primarily B lymphocytes) recombined in their initial proportion in the whole population. Kinetics and dose responses of isoproterenol-induced cyclic AMP were evaluated for each population. Maximal responses for all populations except the RFC-depleted population occurred at 5 and 12 min; the RFC-depleted population showed equal response at all incubation periods. Significant differences (p < 0.01) between the RFC-rich + -depleted population occurred at 5 and 12 min but not at 30 min. The RFC-rich population showed consistently greater cyclic AMP stimulation than the RFC-depleted population (p < 0.025) at 10⁻⁵ M (377% compared with 74% above baseline), 10⁻⁴ M (347% compared with 56%), and 10⁻³ M (400% compared with 80%) isoproterenol. No consistent differences were found between the whole and recombination populations at any dose of isoproterenol, suggesting no marked effect of the separation procedure itself. Propranolol at 1 × 10⁻⁴ M inhibited the isoproterenol stimulation of each population. The use of a phosphodiesterase inhibitor did not change the differences observed between RFC-rich and -depleted populations. These data suggest that striking heterogeneity of beta adrenergic responses exist between T lymphocytes and a B cell-enriched lymphocyte population. Studies evaluating beta adrenergic function in man must consider the suitability of this cell type because of the heterogeneity of peripheral blood lymphocyte subpopulations.