Identification and Characterization of Human Activation-Induced ChAT+CD4+ T Cells

Abstract

Vasodilation is a cornerstone of inflammation physiology. By regulating vasodilation and tissue entry of T cells, CD4+ T lymphocytes expressing choline acetyltransferase (ChAT), a key enzyme for biosynthesis of the vasorelaxant acetylcholine (ACh), critically link immunity with vascular biology in mice. However, the characterization of primary human ChAT+ T cells remained elusive. Here, we identified human ChAT+ T cells and report that ChAT mRNA was induced by activation. Functional studies demonstrated that T cell-derived ACh increased muscarinic ACh-receptor dependent NO-synthase activity and vasorelaxation. Further, single-cell RNA-sequencing revealed ChAT+CD4+ T cells in blood from patients with severe circulatory failure and a high relative frequency of ChAT+CD4+ T cells correlated with better 30-day survival in this cohort. Our findings provide the first insights into ChAT biology in primary human T cells, linking ChAT+ T cells with vasorelaxation as well as survival in a cohort of critically ill patients.