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

Maureen A Cox; Gordon S Duncan; Gloria H Y Lin; Benjamin E Steinberg; Lisa X Yu; Dirk Brenner; Luke N Buckler; Andrew J Elia; Andrew C Wakeham; Brian Nieman; Carmen Dominguez-Brauer; Alisha R Elford; Kyle T Gill; Shawn P Kubli; Jillian Haight; Thorsten Berger; Pamela S Ohashi; Kevin J Tracey; Peder S Olofsson; Tak W Mak

doi:10.1126/science.aau9072

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

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

Authors

Maureen A Cox¹, Gordon S Duncan¹, Gloria H Y Lin¹, Benjamin E Steinberg^{1

2}, Lisa X Yu³, Dirk Brenner^{1

4

5}, Luke N Buckler¹, Andrew J Elia¹, Andrew C Wakeham¹, Brian Nieman^{3

6}, Carmen Dominguez-Brauer¹, Alisha R Elford¹, Kyle T Gill¹, Shawn P Kubli¹, Jillian Haight¹, Thorsten Berger¹, Pamela S Ohashi^{1

7}, Kevin J Tracey⁸, Peder S Olofsson^{8

9}, Tak W Mak^{10

6

7

11}

Affiliations

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD4-Positive T-Lymphocytes / enzymology
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / enzymology
CD8-Positive T-Lymphocytes / immunology*
Cell Movement
Choline O-Acetyltransferase / genetics
Choline O-Acetyltransferase / immunology*
Female
Interleukins / immunology*
Lymphocyte Activation
Lymphocytic Choriomeningitis / immunology*
Lymphocytic choriomeningitis virus
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Vasodilation

Substances

Interleukins
Choline O-Acetyltransferase
interleukin-21

Abstract

Publication types

MeSH terms

Substances

Grants and funding