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

• Published in: Science (American Association for the Advancement of Science) Vol. 363; no. 6427; pp. 639 - 644
• Main Authors: Cox, Maureen A, Duncan, Gordon S, Lin, Gloria H Y, Steinberg, Benjamin E, Yu, Lisa X, Brenner, Dirk, Buckler, Luke N, Elia, Andrew J, Wakeham, Andrew C, Nieman, Brian, Dominguez-Brauer, Carmen, Elford, Alisha R, Gill, Kyle T, Kubli, Shawn P, Haight, Jillian, Berger, Thorsten, Ohashi, Pamela S, Tracey, Kevin J, Olofsson, Peder S, Mak, Tak W
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 08.02.2019
• Subjects: Ablation; Acetylcholine; Acetyltransferase; Animals; CD4 antigen; CD4-Positive T-Lymphocytes - enzymology; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - enzymology; CD8-Positive T-Lymphocytes - immunology; Cell adhesion & migration; Cell Movement; Choline; Choline O-acetyltransferase; Choline O-Acetyltransferase - genetics; Choline O-Acetyltransferase - immunology; Chronic infection; Clonal deletion; Constraining; Enzymes; Female; Immune system; Immunity; Immunology; Infections; Interleukin 21; Interleukins - immunology; Leukocyte migration; Lymphocyte Activation; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphocytic Choriomeningitis - immunology; Lymphocytic choriomeningitis virus; Male; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Mice, Transgenic; Migration; Muscle contraction; Muscles; Muscular function; Tissues; Vasodilation; Viral infections; Viruses
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aau9072

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 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.