Pharmacological modification of immunoregulatory T lymphocytes. I. Effect of adenosine, H1 and H2 histamine agonists upon T lymphocyte regulation of B lymphocyte differentiation in vitro.

ABSTRACT

Human peripheral blood T lymphocytes were fractionated according to the lability of their sheep red blood cell (E) receptors to theophylline. Theophylline sensitive (Ts) cells function as suppressors of pokeweed mitogen induced B cell differentiation into plasma cells, while theophylline resistant (Tr) cells function as helper/inducer cells in this reaction. The Ts fraction is enriched for cells bearing receptors for the Fc portion of IgG (RFc gamma) while the Tr fraction is depleted of RFc gamma bearing cells. Brief exposure of Tr cells to adenosine or impromidine, an H2 histamine agonist, cause a rapid increase in the number of Tr cells bearing RFc gamma and the development of radioresistant suppressor cell activity. The RFc gamma induced on Tr cells by adenosine or impromidine are more stable in culture than the spontaneously occurring RFc gamma on Ts cells. Ts suppressor activity is radiosensitive and exposure of Ts cells to 2(2-pyridyl)ethylamine, an H1 histamine agonist, results in a marked decrease in RFc gamma on Ts cells as well as loss of Ts suppressor activity. These data indicate that RFc gamma expression and the immunoregulatory function of T lymphocyte subsets may be modified by drugs acting upon adenosine, H1 and H2 histamine receptors.