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

Tarnawski, L.; Gallina, A. L.; Kort, E. J.; Shavva, V. S.; Zhuge, Z.; Martinez Enguita, D.; Weiland, M.; Caravaca, A. S.; Schmidt, S.; Wang, F.-H.; Farnert, A.; Weitzberg, E.; Gustafsson, M.; Eberhardson, M.; Hult, H.; Kehr, J.; Malin, S. G.; Carlstrom, M.; Jovinge, S.; Olofsson, P. S.

doi:10.1101/2021.04.27.441632

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bioRxiv · 10.1101/2021.04.27.441632

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

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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.

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Tarnawski, L., Gallina, A. L., Kort, E. J., Shavva, V. S., Zhuge, Z., Martinez Enguita, D., Weiland, M., Caravaca, A. S., Schmidt, S., Wang, F.-H., Farnert, A., Weitzberg, E., Gustafsson, M., Eberhardson, M., Hult, H., Kehr, J., Malin, S. G., Carlstrom, M., Jovinge, S., Olofsson, P. S.. 2021-04-28. Identification and Characterization of Human Activation-Induced ChAT+CD4+ T Cells. https://doi.org/10.1101/2021.04.27.441632

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