Activated T helper 1 and T helper 2 cells differentially express the beta-2-adrenergic receptor: a mechanism for selective modulation of T helper 1 cell cytokine production.
We recently reported that resting clones of murine Th1 cells, but not resting Th2 cells, expressed a detectable level of the beta-2-adrenergic receptor (beta 2AR). In the present study, we proposed that the level of beta 2AR expression on anti-CD3 mAb-activated CD4+ effector Th cells may differ from the level on resting cells, and that a change in receptor expression may alter the functional responsiveness of these cells to either the beta 2AR-selective ligand terbutaline or the sympathetic neurotransmitter norepinephrine. Following anti-CD3 activation, the beta 2AR was expressed on Th1 cells, but not Th2 cells. The number of binding sites on Th1 cells was maintained, with no change in affinity, over a 24-h activation period. When Th clones were exposed to terbutaline following anti-CD3 activation, Th1 cell, but not Th2 cell, cytokine production was modulated. IL-2 production by Th1 cells was decreased, while IFN-gamma production was not significantly altered. The decrease in IL-2 production was concentration dependent and was blocked by an antagonist. In comparison with control supernatants, the lower level of IL-2 present in terbutaline-exposed culture supernatants supported the proliferation of an IL-2-dependent Th1 clone to a lesser degree. Additionally, norepinephrine down-modulates IL-2, but not IFN-gamma, production by binding specifically to the beta-adrenergic receptor. Thus, a detectable level of the beta 2AR is expressed on activated Th1 cells, but not activated Th2 cells, thereby providing a mechanism by which IL-2 production is preferentially modulated by an endogenous and therapeutic ligand following Th1 cell activation.
Ramer-Quinn
D S
DS
Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, IL 60153, USA.
Baker
R A
RA
Sanders
V M
VM
D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009638:Norepinephrine / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis* / Q000502:physiology*; D013726:Terbutaline / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D058666:Adrenergic beta-2 Receptor Agonists; D016207:Cytokines; D007376:Interleukin-2; D018343:Receptors, Adrenergic, beta-2; D013726:Terbutaline; D009638:Norepinephrine