Expression of acetylcholine in lymphocytes and modulation of an independent lymphocytic cholinergic activity by immunological stimulation

Although acetylcholine (ACh) is classically thought of as a neurotransmitter in mammalian species, lymphocytes possess most of the components needed to constitute an independent non-neuronal cholinergic system. These include ACh itself, choline acetyltransferase (ChAT), high-affinity choline transporter, acetylcholinesterase, and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Activation of mAChRs and nAChRs on lymphocytes elicits increases in the intracellular Ca²⁺ concentration and stimulates c-fos gene expression and nitric oxide synthesis. Which subpopulations of T lymphocytes are the source of blood ACh is not yet known, though expression of ChAT mRNA was observed in human peripheral CD⁴⁺ (helper) but not in CD⁸⁺ (cytotoxic) T cells. Stimulation of lymphocytes with phytohemagglutinin, a T-cell activator, or with monoclonal antibodies that bind the CD7 and/orCDl la cell surface molecules activates lymphocytic cholinergic activity, as evidenced by increased synthesis and release of ACh and up-regulation of expression of ChAT and M₅ mAChR mRNA. Abnormalities in the lymphocytic cholinergic system have been detected in spontaneously hypertensive rats and MRL-lpr mice, two animal models of immune disorders. Taken together, these data present a compelling picture in which immune function is, at least in part, under the control of an independent non-neuronal lymphocytic cholinergic system.