Qian_2011_Genes.Immun_12_222

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 alpha5, alpha9, alpha10, beta1, beta2, beta4 nAChR subunits and M(1), M(3), M(4) and M(5) mAChR subtypes, whereas alpha2 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 alpha4 and alpha7, upregulation of alpha5, alpha10, beta4, M(1) and M(5) and downregulation of alpha9 and beta2, whereas in vitro activation of CD8 T cells also featured the appearance of alpha4 and alpha7, as well as upregulation of alpha2, alpha5, beta4, M(1) and M(4), and downregulation of alpha10, beta1, beta2 and M(3). In vitro polarization toward T helper (Th) 1 lineage was associated with a decrease of beta2, beta4 and M(3) expression; that toward Th2 cells with downregulation of alpha9 and M(3), and upregulation of M(1) and M(5); and that toward Th17 phenotype with downregulation of alpha9, alpha10, beta2 and M(3) mAChR. Polarized T cells also expressed alpha4, but not alpha1, alpha2, alpha3, alpha6, beta3 or M(2). 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-gamma (IFN-gamma) and downregulated interleukin (IL)-17 secretion, whereas the muscarinic stimulation enhanced IL-10 and IL-17 and inhibited INF-gamma secretion. These results demonstrated plasticity of the T-cell cholinergic system.