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Science. 2019 Feb 8;363(6427):639-644. doi: 10.1126/science.aau9072.

Choline acetyltransferase-expressing T cells are required to control chronic viral infection.

Author information

1
The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
2
Department of Anesthesia, University of Toronto, Toronto, ON M5G 1E2, Canada.
3
Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON M5T 3H7, Canada.
4
Department of Infection and Immunity, Luxembourg Institute of Health, L-4354 Esch-sur-Alzette, Luxembourg.
5
Odense Research Center for Anaphylaxis (ORCA), Department of Dermatology and Allergy Center, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
6
Ontario Institute for Cancer Research and Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2C1, Canada.
7
Department of Immunology, University of Toronto, Toronto, ON M5G 2C1, Canada.
8
Laboratory of Biomedical Science, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
9
Center for Bioelectronic Medicine, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
10
The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. tmak@uhnresearch.ca.
11
Department of Pathology, University of Hong Kong, Hong Kong.

Abstract

Although widely studied as a neurotransmitter, T cell-derived acetylcholine (ACh) has recently been reported to play an important role in regulating immunity. However, the role of lymphocyte-derived ACh in viral infection is unknown. Here, we show that the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production, is robustly induced in both CD4+ and CD8+ T cells during lymphocytic choriomeningitis virus (LCMV) infection in an IL-21-dependent manner. Deletion of Chat within the T cell compartment in mice ablated vasodilation in response to infection, impaired the migration of antiviral T cells into infected tissues, and ultimately compromised the control of chronic LCMV clone 13 infection. Our results reveal a genetic proof of function for ChAT in T cells during viral infection and identify a pathway of T cell migration that sustains antiviral immunity.

PMID:
30733420
DOI:
10.1126/science.aau9072

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