| First Author | Estrada LD | Year | 2016 |
| Journal | Eur J Immunol | Volume | 46 |
| Issue | 8 | Pages | 1948-58 |
| PubMed ID | 27222010 | Mgi Jnum | J:252104 |
| Mgi Id | MGI:5923768 | Doi | 10.1002/eji.201646395 |
| Citation | Estrada LD, et al. (2016) Sympathetic neural signaling via the beta2-adrenergic receptor suppresses T-cell receptor-mediated human and mouse CD8(+) T-cell effector function. Eur J Immunol 46(8):1948-58 |
| abstractText | 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 beta2-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 beta2-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. |
