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.


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


  • Interleukins
  • Choline O-Acetyltransferase
  • interleukin-21