Beta-agonists Modulate T-cell Functions Via Direct Actions on Type 1 and Type 2 Cells.
From: Department of Internal Medicine, Center for Human Genomics, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA.
Blood
- Publish Date: Mar 2006
- ISSN: 0006-4971
- Volume: 107
- Issue: 5
- Pages: 2052-60
- Medium: Print
- Language: English
- Citation (JAMA): Loza Matthew J, Foster Susan, Peters Stephen P, et al. Beta-agonists Modulate T-cell Functions Via Direct Actions on Type 1 and Type 2 Cells.. Blood Mar 2006;107:2052-60
Abstract
Although the beta2-adrenergic receptor (beta2AR) is the most extensively characterized G-protein-coupled receptor (GPCR), the effects of beta-agonists on T-cell subtype function remain poorly understood. In contrast to studies suggesting lack of beta2AR expression on type 2 T cells, we demonstrate that type 2 interleukin-13+ (IL-13+) T cells (CD4+ or CD8+) in human peripheral blood lymphocytes (PBLs) can respond directly to beta-agonist, with effects including induction of protein kinase A (PKA) activity and associated inhibition of CD3-stimulated CD25 expression; CD3-stimulated IL-13, interferon-gamma (IFN-gamma), and IL-2 production; and p38 mitogen-activated protein kinase (MAPK) phosphorylation. PGE2 was more efficacious than beta-agonist in activating PKA and inhibiting cytokine production. beta-agonist and PGE2 also inhibited phorbol myristate acetate (PMA) + calcimycin-stimulated IFN-gamma and IL-2 (but not IL-13) production, suggesting that upstream CD3-initiated signaling is not the sole locus of PKA actions. Differential regulation of PMA-stimulated p38, p42/p44, and NF-kappaB explained the capacity of PGE2 and beta-agonist to inhibit IFN-gamma but not IL-13 production. The inhibition of CD3 + CD28-stimulated IL-13 production by both beta-agonist and PGE2 was reversed at low agonist concentrations, resulting in enhanced IL-13, but not IFN-gamma or IL-2, production. These findings identify direct effects of beta2AR activation on T-cell subtypes and suggest a complex role for GPCRs and PKA activity in modulating T-cell functions.
Mesh Headings (Keywords): Adrenergic beta-Agonists, Animals, Antigens, CD, CD8-Positive T-Lymphocytes, Calcimycin, Carcinogens, Cells, Cultured, Cytokines, Dinoprostone, Humans, Ionophores, Lymphocyte Activation, MAP Kinase Signaling System, NF-kappa B, Oxytocics, Protein Kinases, Receptors, Adrenergic, beta-2, Tetradecanoylphorbol Acetate, Th1 Cells, Th2 Cells
Check for Full Text / PubMed Unique Identifier (PMID): 16278302
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