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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2052-2060. Prepublished online as a Blood First Edition Paper on November 8, 2005; DOI 10.1182/blood-2005-08-3265. This Article Full Text (PDF) All Versions of this Article: 2005-08-3265v1 107/5/2052    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Loza, M. J Articles by Penn, R. B Search for Related Content PubMed PubMed Citation Articles by Loza, M. J Articles by Penn, R. B Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 12, 2005 Accepted October 24, 2005 Beta-agonists modulate T cell functions via direct actions on type 1 and type 2 cells Matthew J Loza, Susan Foster, Stephen P Peters, and Raymond B Penn* Department of Internal Medicine, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA * Corresponding author; email: rpenn{at}wfubmc.edu. Although the 2-adrenergic receptor (2AR) is the most extensively characterized G-protein coupled receptor (GPCR), the effects of -agonists on T cell subtype function remain poorly understood. In contrast to studies suggesting lack of 2AR expression on type 2 T cells, we demonstrate that type 2 IL-13+ T cells(CD4+ or CD8+) in human PBL respond directly to -agonist, with effects including induction of PKA activity, and associated inhibition of: 1) CD3-stimulated CD25 expression; 2) CD3-stimulated IL-13, IFN- and IL-2 production; and 3) p38 MAPK phosphorylation. PGE2 was more efficacious than -agonist in activating PKA and inhibiting cytokine production. -agonist and PGE2 also inhibited PMA+Calcimycin-stimulated IFN- 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-B explained the capacity of PGE2 and -agonist to inhibit IFN- but not IL-13 production. The inhibition of CD3+CD28-stimulated IL-13 production by both -agonist and PGE2 was reversed at low agonist concentrations, resulting in enhanced IL-13, but not IFN- or IL-2, production. These findings identify direct effects of 2AR activation on T cell subtypes and suggest a complex role for GPCRs and PKA activity in modulating T cell functions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Kern and T. Ziemssen Review: Brain immune communication psychoneuroimmunology of multiple sclerosis Multiple Sclerosis, January 1, 2008; 14(1): 6 - 21. [Abstract] [PDF] D. A. Deshpande, R. M. Pascual, S.-W. Wang, D. M. Eckman, E. C. Riemer, C. D. Funk, and R. B. Penn PKC-dependent regulation of the receptor locus dominates functional consequences of cysteinyl leukotriene type 1 receptor activation FASEB J, August 1, 2007; 21(10): 2335 - 2342. [Abstract] [Full Text] [PDF] R. B. Penn, V. E. Ortega, and E. R. Bleecker A Roadmap to functional genomics Physiol Genomics, June 19, 2007; 30(1): 82 - 88. [Abstract] [Full Text] [PDF] L. M. DeFord-Watts, J. A. Young, L. A. Pitcher, and N. S. C. van Oers The Membrane-proximal Portion of CD3 {epsilon} Associates with the Serine/Threonine Kinase GRK2 J. Biol. Chem., June 1, 2007; 282(22): 16126 - 16134. [Abstract] [Full Text] [PDF] D. Peter, S. L. C. Jin, M. Conti, A. Hatzelmann, and C. Zitt Differential Expression and Function of Phosphodiesterase 4 (PDE4) Subtypes in Human Primary CD4+ T Cells: Predominant Role of PDE4D J. Immunol., April 15, 2007; 178(8): 4820 - 4831. [Abstract] [Full Text] [PDF]

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