Objective: Dopamine, a catecholamine neurotransmitter, influences growth and proliferation of lymphocytes. Pharmacological doses of dopamine have been shown to modulate T cell functions significantly, but no information is available on the effect of physiological concentrations of circulating dopamine on CD4+ and CD8+ T cell functions. This information may be of importance since significantly elevated plasma dopamine levels were observed in humans during uncoping stress, and suppression of T cell functions during stress is a well-known phenomenon. However, the mechanism inducing the suppression of T cell functions during stress is not yet clear. In the present investigation, we evaluated the effect of the dopamine level attained in the plasma of individuals with uncoping stress on the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. Methods: T cell subpopulations were separated by panning. The effect of dopamine on IL-2-induced cell proliferation in vitro was evaluated by [³H]thymidine incorporation and cytotoxicity by ⁵¹Cr release, receptors by radioligand binding, cAMP by an assay kit and apoptosis by DNA fragmentation. Results: At these elevated physiological concentrations, dopamine was found to inhibit significantly the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. This dopamine-mediated 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-receptor-mediated stimulation of intracellular cAMP. Conclusion: Results may be of significance to understand the role of peripheral dopamine in human neuroimmune communication in terms of physiological homeostasis in health and disease.

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Background The physiological functions of neurotrophins occur through binding to two different receptors: pan75 neurotrophin receptor (p75NTR) and a family of tropomysin receptor kinases (Trks A, B, and C). Recently, we reported that expression of neurotrophins and TrkB were reduced in brains of suicide subjects. Present study examines whether expression and activation of Trk receptors and expression of p75NTR are altered in brain of these subjects. Methods Expression levels of TrkA, B, C, and of p75NTR were measured by quantitative RT-PCR and Western blot in prefrontal cortex (PFC) and hippocampus of suicide and normal control subjects. The activation of Trks was determined by immunoprecipitation followed by Western blotting using phosphotyrosine antibody. Results In hippocampus, lower mRNA levels of TrkA and TrkC were observed in suicide subjects. In the PFC, the mRNA level of TrkA was decreased, without any change in TrkC. On the other hand, the mRNA level of p75NTR was increased in both PFC and hippocampus. Immunolabeling studies showed similar results as observed for the mRNAs. In addition, phosphorylation of all Trks was decreased in hippocampus, but in PFC, decreased phosphorylation was noted only for TrkA and B. Increased expression ratios of p75NTR to Trks were also observed in PFC and hippocampus of suicide subjects. Conclusions Our results suggest not only reduced functioning of Trks in brains of suicide subjects but that increased ratios of p75NTR to Trks indicate possible activation of pathways that are apoptotic in nature. These findings may be crucial in the pathophysiology of suicide.

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