Selective β-adrenergic Receptor Expression on Human Memory CD8+ T Lymphocyte Subsets Regulates Mobilization and INF-y Production

Introduction: CD8⁺ T lymphocytes (CD8TLs) express β-adrenergic receptors (βAR), which bind the neurotransmitter norepinephrine and stress hormone epinephrine released during inflammation, trauma, and psychological stress. Little is known about the functions of this βAR expression on CD8TLs. Methods: Volunteers were exposed to a psychological stressor (N=24). Flow cytometry identified CD8TL subsets by CCR7, CD27, CD28 and CD45RA expression. Adrenergic receptor subtype expression was determined by micro-array. The effects of βPAR stimulation on IFN-γ production in activated CD8TLs was tested in vitro using PMA/Ionomycin. Results: Stress caused selective migration of effector-memory (CCR7⁻CD27⁻CD28⁻) CD8TLs into the blood (+148%, p<.001). An 8-fold up-regulation of the β₂AR was demonstrated in effector-memory cells as compared to naïve CD8TLs. Stimulation of the β₂AR subtype completely inhibited IFN-γ production. Conclusion: These results show that β₂AR stimulation enhances peripheral immune surveillance in a highly selective manner, and might protect against excessive cytokine release during inflammation and stress.