HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.08-107458v1 22/10/3491    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 Google Scholar Articles by Csóka, B. Articles by Haskó, G. PubMed PubMed Citation Articles by Csóka, B. Articles by Haskó, G.

Adenosine A_2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function

Balázs Csóka^*, Leonóra Himer, Zsolt Selmeczy, E. Sylvester Vizi, Pál Pacher, Catherine Ledent, Edwin A. Deitch^*, Zoltán Spolarics^*, Zoltán H. Németh^*,|| and György Haskó^*,,1

^* Department of Surgery, University of Medicine and Dentistry New Jersey, New Jersey Medical School, Newark, New Jersey, USA;

Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary;

Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA;

Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Université Libre de Bruxelles, Brussels, Belgium; and

^|| Department of Surgery, Morristown Memorial Hospital, Morristown, New Jersey, USA

¹ Correspondence: György Haskó, Department of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Ave., University Heights, Newark, NJ 07103, USA. E-mail: haskoge{at}umdnj.edu

Adenosine is an immunosuppressive nucleoside, and adenosine A_2A receptors inhibit T-cell activation. We investigated the role of A_2A receptors in regulating T helper (Th)1- and Th2-cell development and effector function. A_2A-receptor stimulation suppressed the development of T-cell receptor (TCR) -stimulated naive T cells into both Th1 and Th2 cells, as indicated by decreased IFN- production by cells developed under Th1-skewing conditions and decreased interleukin (IL) -4, IL-5, and IL-10 production by cells developed under Th2-skewing conditions. Using A_2A receptor-deficient mice, we demonstrate that A_2A receptor activation inhibits Th1- and Th2-cell development by decreasing the proliferation and IL-2 production of naive T cells, irrespective of whether the cells are expanded under Th1- or Th2-skewing environment. Using in vivo established Th1 and Th2 cells, we further demonstrate the nonselective nature of A_2A receptor-mediated immunosuppressive effects, because A_2A receptor activation decreased IFN- and IL-4 secretion and mRNA level of TCR-stimulated effector Th1 and Th2 cells, respectively. A_2A receptor mRNA expression in both Th1 and Th2 effector cells increased following TCR stimulation. In summary, these data demonstrate that A_2A receptor activation has strong inhibitory actions during early developmental, as well as late effector, stages of Th1- and Th2-cell responses.—Csóka, B., Himer, L., Selmeczy, Z., Vizi, E. S., Pacher, P., Ledent, C., Deitch, E. A., Spolarics, Z., Németh, Z. H., Haskó, G. Adenosine A_2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function.

Key Words: autoimmunity • allergy • inflammation • rheumatoid arthritis • spleen and lymph nodes