title: Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function.
abstract: 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-gamma 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-gamma 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.
authors.affiliation: Department of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Ave., University Heights, Newark, NJ 07103, USA.
authors.forename: Balázs
authors.initials: B
authors.lastname: Csóka
authors.forename: Leonóra
authors.initials: L
authors.lastname: Himer
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Selmeczy
authors.forename: E Sylvester
authors.initials: ES
authors.lastname: Vizi
authors.forename: Pál
authors.initials: P
authors.lastname: Pacher
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Spolarics
authors.forename: Zoltán H
authors.initials: ZH
authors.lastname: Németh
authors.forename: György
authors.initials: G
authors.lastname: Haskó
mesh_terms: D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D017252:CD3 Complex; D015704:CD4 Antigens; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D015847:Interleukin-4; D007371:Interferon-gamma