Beta Adrenoceptor Modulation of the Generation of Murine Cytotoxic T Lymphocytes in Vitro

The effects of stimulating beta adrenoceptors on lymphocytes during the generation of cell-mediated immunity were examined. In an in vitro system for the generation of murine cell-mediated cytotoxicity, addition of isoproterenol (10(-7) M), epinephrine (10(-6) M) or norepinephrine (10(-4) M) enhanced the number of lytic units generated compared to control cultures. This increase was blocked by dl-propranolol (5 X 10(-6) M). I-Propranolol (10(-11) to 10(-7) M) blocked the isoproterenol-induced increase in lytic units per culture, but d-propranolol (10(-11) to 10(-7) M) did not. Terbutaline (10(-5) M), a relatively selective beta-2 agonist, similarly augmented the generation of cell-mediated cytotoxicity, with the increase again blocked by propranolol. Butoxamine (5 X 10(-6) M), a beta-2 antagonist, but not atenolol (5 X 10(-6) M), a beta-1 antagonist, blocked the epinephrine-induced increase in cell-mediated cytotoxicity. Addition of phentolamine (5 X 10(-6) M) had no effect on the epinephrine-induced increase in lytic units per culture. However, in the presence of phentolamine, norepinephrine increased lytic units per culture to a greater degree than that seen with norepinephrine alone, suggesting a balance between positive beta effects and inhibitory alpha effects upon simultaneous alpha and beta stimulation. These data provide further evidence for an immunoenhancing role of beta receptor stimulation during the generation of immune responses.