Differential expression of the beta2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help.

Abstract

An important function of the sympathetic nervous system is to maintain homeostasis by modulating the level of cellular activity in many diverse organ systems. The sympathetic neurotransmitter norepinephrine modulates the level of T and B lymphocyte activity by binding to the beta2-adrenergic receptor (beta2AR). The present study was designed to elucidate the mechanism by which stimulation of the beta2AR affects both Th1/Th2 cell cytokine production and Th1/Th2 cell-dependent Ab production. Clones of murine Th1/Th2 cells were exposed to the beta2AR agonist terbutaline before activation by Ag-presenting B cells. Terbutaline exposure of Th1 cells before activation inhibited IFN-gamma production by Th1 cells and subsequent IgG2a production by B cells. IgG2a inhibition was prevented by addition of the betaAR antagonist nadolol or exogenous IFN-gamma. In contrast to Th1 cells, terbutaline did not affect either IL-4 production by Th2 cells or subsequent IgG1 production by B cells. Although baseline levels of intracellular cAMP were similar in both subsets, terbutaline induced an increase in cAMP levels in Th1 cells only. Radioligand binding studies showed that a detectable number of beta2AR binding sites were present on Th1 cells, but not on Th2 cells. Immunofluorescence analyses showed that Th1 cells expressed a higher level of the beta2AR cytoplasmic carboxyl terminus than did Th2 cells. These results show that expression of the beta2AR binding site by Th1 cells, but not by Th2 cells, establishes a physiologic mechanism for selective modulation of Th1 cell IFN-gamma production and IFN-gamma-dependent IgG2a production, provided that beta2AR stimulation occurs before cell activation by a B cell.

The β1-Adrenergic Receptor Contributes to Sepsis-Induced Immunosuppression Through Modulation of Regulatory T-Cell Inhibitory Function*

“…In both innate and adaptive immune cells, adrenergic receptors are widely expressed though not well characterized, particularly for the β subtype (34). Numerous studies have demonstrated the presence of β-AR on almost all lymphocyte subtypes (35)(36)(37). However, until recently, only β 2 -AR but not β 1 -AR subtypes were found on T cells (38,39).…”

Autonomic control of inflammation

“…We speculate that the combination of these immunomodulating effects mediated by β2‐adrenergic receptors might contribute to the suppression of inflammatory responses. Stimulation of β2‐adrenergic receptors was shown to inhibit differentiation and functions of T helper (Th1) type 1 cells in vitro . However, in our experimental system, in vivo differentiation of Th cells was not affected by agonist stimulation or deficiency of β2‐adrenergic receptors .…”

“…Stimulation of b2-adrenergic receptors was shown to inhibit differentiation and functions of T helper (Th1) type 1 cells in vitro. 37,38 However, in our experimental system, in vivo differentiation of Th cells was not affected by agonist stimulation or deficiency of b2-adrenergic receptors. 34 Thus, it is unlikely that alternation of Th cell differentiation could contribute to the suppressed inflammation, at least in our experiments.…”

Control of lymphocyte trafficking and adaptive immunity by adrenergic nerves

“…3 Additionally, stimulation of b 2 AR was shown to regulate differentiation and functions of helper T (Th) cells in vitro. 4,5 These findings showed that inputs from adrenergic nerves can directly act on immune cells and alter their behaviors.…”

“…Pharmacological studies carried out in the same period showed that noradrenaline bound to the surface of lymphocytes, which was almost exclusively mediated by β 2 ‐adrenergic receptors (β 2 AR) . Additionally, stimulation of β 2 AR was shown to regulate differentiation and functions of helper T (Th) cells in vitro . These findings showed that inputs from adrenergic nerves can directly act on immune cells and alter their behaviors.…”