Human CD4+CD25+ regulatory T cells selectively express tyrosine hydroxylase and contain endogenous catecholamines subserving an autocrine/paracrine inhibitory functional loop.

摘要: CD4+CD25+ regulatory T lymphocytes (Tregs) are specialized cells playing a key role in the control of immune homeostasis. Here, we show that human Tregs constitutively express tyrosine hydroxylase (TH, EC 1.14.16.2), rate-limiting enzyme synthesis catecholamines, and contain substantial amounts dopamine, norepinephrine, epinephrine, which released upon treatment with reserpine. Catecholamine release results reduced production interleukin-10 transforming growth factor-beta by Tregs, down-regulation Treg-dependent inhibition effector T-lymphocyte (Teff) proliferation, occurs without affecting tumor necrosis factor-alpha or interferon-gamma. Teffs on cell membrane both D1-like D2-like dopaminergic receptors to similar extent (12%-29% cells). Catecholamine-dependent is, however, selectively reversed pharmacological blockade receptors, only (and not Teffs) also expressed at level mRNA functionally coupled intracellular cAMP. These findings indicate endogenous catecholamines subserve an autocrine/paracrine loop involving pathways resulting Treg function.