Physiological concentrations of dopamine inhibit the proliferation and cytotoxicity of human CD4+and CD8+T cells in vitro: A receptor-mediated mechanism

Objective: Dopamine, a catecholamine neurotransmitter, influences growth an d proliferation of lymphocytes. Pharmacological doses of dopamine have been shown to modulate T cell functions significantly, but no information is av ailable on the effect of physiological concentrations of circulating dopami ne on CD4+ and CD8+ T cell functions. This information may be of importance since significantly elevated plasma dopamine levels were observed in human s during uncoping stress, and suppression of T cell functions during stress is a well-known phenomenon. However, the mechanism inducing the suppressio n of T cell functions during stress is not yet clear. In the present invest igation, we evaluated the effect of the dopamine level attained in the plas ma of individuals with uncoping stress on the proliferation and cytotoxicit y of CD4+ and CD8+ T cells in vitro. Methods: T cell subpopulations were se parated by panning. The effect of dopamine on IL-2-induced cell proliferati on in vitro was evaluated by [H-3]thymidine incorporation and cytotoxicity by Cr-51 release, receptors by radioligand binding, cAMP by an assay kit an d apoptosis by DNA fragmentation. Results: At these elevated physiological concentrations, dopamine was found to inhibit significantly the proliferati on and cytotoxicity of CD4+ and CD8+ T cells in vitro. This dopamine-mediat ed inhibition of proliferation was more marked on CD8+ T cells than on CD4 T cells. The underlying mechanism was found to be D1 class of dopamine-rec eptor-mediated stimulation of intracellular cAMP. Conclusion: Results may b e of significance to understand the role of peripheral dopamine in human ne uroimmune communication in terms of physiological homeostasis in health and disease. Copyright 2001 S. Karger AG, Basel.