NEUROTRANSMITTER SUPPRESSION OF THE IN-VITRO GENERATION OF A CYTOTOXIC T-LYMPHOCYTE RESPONSE AGAINST THE SYNGENEIC MOPC-315 PLASMACYTOMA

We have previously shown that, as a consequence of low-dose melphalan (L-phenylalanine mustard (L-PAM) therapy, the hitherto immunosuppresse d spleen cells from BALB/c mice bearing a large MOPC-315 tumor (in con trast to spleen cells from normal mice) acquire the ability to generat e a greatly enhanced anti-MOPC-315 cytotoxic T lymphocyte (CTL) respon se upon in vitro stimulation with MOPC-315 tumor cells. Here we show t hat the catecholamines norepinephrine, epinephrine, and isoproterenol suppressed the in vitro generation of anti-MOPC-315 cytotoxicity by sp leen cells from mice that had just completed the eradication of a larg e MOPC-315 tumor following low-dose L-PAM therapy (L-PAM TuB spleen ce lls), as well as by spleen cells from normal mice. In contrast to the marked suppression obtained with catecholamines, the cholinergic agoni st carbachol had no effect on the in vitro generation of splenic anti- MOPC-315 cytotoxicity. The inhibitory effect of the catecholamines was ''mimicked'' by the membrane-penetrating analog of cAMP, dibutyryl-cA MP, and by cholera toxin at concentrations that stimulate the endogeno us production of cAMP. The beta-adrenergic receptor antagonist propran olol did not block norepinephrine-induced inhibition of the generation of anti-MOPC-315 cytotoxicity by either normal or L-PAM TuB spleen ce lls. Since the curative effectiveness of low-dose L-PAM therapy for MO PC-315 tumor bearers requires the participation of CD8(+) T cells that exploit a CTL response in tumor eradication, it is conceivable that n orepinephrine may reduce the therapeutic outcome of low-dose chemother apy by inhibiting the acquisition of CTL activity.