Differential expression of the beta2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help.
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.
Sanders
V M
VM
Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, IL 60153, USA. vsander@luc.edu
Baker
R A
RA
Ramer-Quinn
D S
DS
Kasprowicz
D J
DJ
Fuchs
B A
BA
Street
N E
NE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002999:Clone Cells; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010869:Pindolol / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013726:Terbutaline / Q000494:pharmacology; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D016207:Cytokines; D007074:Immunoglobulin G; D018343:Receptors, Adrenergic, beta-2; D015847:Interleukin-4; D007371:Interferon-gamma; D010869:Pindolol; D000242:Cyclic AMP; D013726:Terbutaline