期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 46, 期 8, 页码 1948-1958出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201646395
关键词
beta 2-Adrenergic receptor; CD8(+) T cells; Cytokine; Cytolysis; Norepinephrine
类别
资金
- NIAID NIH HHS [R56 AI125545, R01 AI056222, T32 AI005284] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008203] Funding Source: Medline
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 beta 2-adrenergic receptor (ADRB2) on primary human CD8(+) effector memory T cells. Treatment of both human and murine CD8(+) T cells with NE decreased IFN-gamma and TNF-alpha secretion and suppressed their cytolytic capacity in response to T-cell receptor (TCR) activation. The effects of NE were specifically reversed by beta 2-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-gamma 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.
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