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

February 08, 2019 By:
  • Cox MA
  • Duncan GS
  • Lin GHY
  • Steinberg BE
  • Yu LX
  • Brenner D
  • Buckler LN
  • Elia AJ
  • Wakeham AC
  • Nieman B
  • Dominguez-Brauer C
  • Elford AR
  • Gill KT
  • Kubli SP
  • Haight J
  • Berger T
  • Ohashi PS
  • Tracey KJ
  • Olofsson PS
  • Mak TW.

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.

2019 Feb. Science.363(6427):639-644.
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