Regulation of CD8 + cytolytic T lymphocyte differentiation by a cholinergic pathway

In this report, we provide evidence that muscarinic receptors play a role in the generation of CD8 + cytolytic T lymphocytes. Analysis of mice with targeted deletions of each of the known muscarinic receptors (M 1–M 5) showed that CD8 + T cells from M 1 receptor-deficient mice had a defect in the ability to differentiate into cytolytic T lymphocytes. Additional pharmacological experiments support the role of muscarinic receptors in wild type mice and suggest that acetylcholine may be involved. Together, these findings suggest that the M 1 muscarinic receptor is involved in CTL development, thus providing novel insights into CD8 + T cell biology and the potential role of cholinergic signaling in immune regulation.