Sympathetic neural signaling via the β2-adrenergic receptor suppresses T-cell receptor-mediated human and mouse CD8+ T-cell effector function

Leonardo D. Estrada, Didem Ağaç, J. David Farrar

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Postganglionic sympathetic neurons innervate secondary lymphoid organs and secrete norepinephrine (NE) as the primary neurotransmitter. NE binds and signals through five distinct members of the adrenergic receptor family. In this study, we show elevated expression of the β2-adrenergic receptor (ADRB2) on primary human CD8+ effector memory T cells. Treatment of both human and murine CD8+ T cells with NE decreased IFN-γ and TNF-α secretion and suppressed their cytolytic capacity in response to T-cell receptor (TCR) activation. The effects of NE were specifically reversed by β2-specific antagonists. Adrb2−/− CD8+ T cells were completely resistant to the effects of NE. Further, the ADRB2-specific pharmacological ligand, albuterol, significantly suppressed effector functions in both human and mouse CD8+ T cells. While both TCR activation and stimulation with IL-12 + IL-18 were able to induce inflammatory cytokine secretion, NE failed to suppress IFN-γ secretion in response to IL-12 + IL18. Finally, the long-acting ADRB2-specific agonist, salmeterol, markedly reduced the cytokine secretion capacity of CD8+ T cells in response to infection with vesicular stomatitis virus. This study reveals a novel intrinsic role for ADRB2 signaling in CD8+ T-cell function and underscores the novel role this pathway plays in adaptive T-cell responses to infection.

Original languageEnglish (US)
Pages (from-to)1948-1958
Number of pages11
JournalEuropean Journal of Immunology
Volume46
Issue number8
DOIs
StatePublished - Aug 1 2016

Fingerprint

T-Cell Antigen Receptor
Adrenergic Receptors
Norepinephrine
T-Lymphocytes
Interleukin-18
Interleukin-12
Cytokines
Vesicular Stomatitis
Albuterol
Infection
Neurotransmitter Agents
Pharmacology
Ligands
Viruses
Neurons

Keywords

  • CD8 T cells
  • Cytokine
  • Cytolysis
  • Norepinephrine
  • β2-Adrenergic receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Medicine(all)

Cite this

Sympathetic neural signaling via the β2-adrenergic receptor suppresses T-cell receptor-mediated human and mouse CD8+ T-cell effector function. / Estrada, Leonardo D.; Ağaç, Didem; Farrar, J. David.

In: European Journal of Immunology, Vol. 46, No. 8, 01.08.2016, p. 1948-1958.

Research output: Contribution to journalArticle

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