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

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

in 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 / Mice / Mice, Inbred C57BL / Mice, Transgenic / Migration / Muscle contraction / Muscles / Muscular function / Vasodilation / Viral infections / Viruses

2019

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

2019

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

2019

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Journal Article

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

Cox, Maureen A.,

Ohashi, Pamela S.,

Berger, Thorsten,

Dominguez-Brauer, Carmen,

Buckler, Luke N.,

Elford, Alisha R.,

Lin, Gloria H. Y.,

Kubli, Shawn P.,

Haight, Jillian,

Tracey, Kevin J.,

Olofsson, Peder S.,

Mak, Tak W.,

Yu, Lisa X.,

Elia, Andrew J.,

Steinberg, Benjamin E.,

C. Wakeham, Andrew,

Gill, Kyle T.,

Brenner, Dirk,

Nieman, Brian,

Duncan, Gordon S.

2019

Overview

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.

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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

/ Animals

/ CD4-Positive T-Lymphocytes - enzymology

/ CD4-Positive T-Lymphocytes - immunology