Adenosine A2A 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, György Haskó

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Adenosine is an immunosuppressive nucleoside, and adenosine A2A receptors inhibit T-cell activation. We investigated the role of A2A receptors in regulating T helper (Th)1- and Th2-cell development and effector function. A2A-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-γ 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 A2A receptor-deficient mice, we demonstrate that A2A 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 A2A receptor-mediated immunosuppressive effects, because A2A receptor activation decreased IFN-γ and IL-4 secretion and mRNA level of TCR-stimulated effector Th1 and Th2 cells, respectively. A2A receptor mRNA expression in both Th1 and Th2 effector cells increased following TCR stimulation. In summary, these data demonstrate that A2A receptor activation has strong inhibitory actions during early developmental, as well as late effector, stages of Th1- and Th2-cell responses.

Original languageEnglish
Pages (from-to)3491-3499
Number of pages9
JournalFASEB Journal
Volume22
Issue number10
DOIs
Publication statusPublished - Oct 2008

Keywords

  • Allergy
  • Autoimmunity
  • Inflammation
  • Rheumatoid arthritis
  • Spleen and lymph nodes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Adenosine A<sub>2A</sub> receptor activation inhibits T helper 1 and T helper 2 cell development and effector function'. Together they form a unique fingerprint.

  • Cite this

    Csóka, B., Himer, L., Selmeczy, Z., Vizi, E. S., Pacher, P., Ledent, C., Deitch, E. A., Spolarics, Z., Németh, Z. H., & Haskó, G. (2008). Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function. FASEB Journal, 22(10), 3491-3499. https://doi.org/10.1096/fj.08-107458