Abstract
Acetylcholine (ACh) regulates vital functions of T cells by acting on the nicotinic and muscarinic classes of cholinergic receptors, nAChR and mAChRs, respectively. This study was performed in murine splenic T cells. In freshly isolated CD4 and CD8 T cells, we detected mRNAs encoding α5, α9, α10, β1, β2, β4 nAChR subunits and M&sub1;, M&sub3;, M&sub4; and M₅ mAChR subtypes, whereas α2 was detected only in CD8 T cells. In vitro activation of CD4 T cells through T-cell receptor (TCR)/CD3 cross-linking was associated with the appearance of α4 and α7, upregulation of α5, α10, β4, M&sub1; and M₅ and downregulation of α9 and β2, whereas in vitro activation of CD8 T cells also featured the appearance of α4 and α7, as well as upregulation of α2, α5, β4, M&sub1; and M&sub4;, and downregulation of α10, β1, β2 and M&sub3;. In vitro polarization toward T helper (Th) 1 lineage was associated with a decrease of β2, β4 and M&sub3; expression; that toward Th2 cells with downregulation of α9 and M&sub3;, and upregulation of M&sub1; and M₅; and that toward Th17 phenotype with downregulation of α9, α10, β2 and M&sub3; mAChR. Polarized T cells also expressed α4, but not α1, α2, α3, α6, β3 or M&sub2;. To determine the role of cholinergic receptors in mediating the immunoregulatory action of autocrine/paracrine ACh, we analyzed the effects of nicotinic and muscarinic agonists±antagonists on cytokine production in the CD4+CD62L+ T cells co-stimulated via TCR/CD3 cross-linking. The nicotinergic stimulation upregulated interferon-γ (IFN-γ) and downregulated interleukin (IL)-17 secretion, whereas the muscarinic stimulation enhanced IL-10 and IL-17 and inhibited INF-γ secretion. These results demonstrated plasticity of the T-cell cholinergic system.