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PMID: 18625677 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology ·Vol. 22 ·No. 10 ·2008-10-00 ·Pages 3491-9

Csóka B, Himer L, Selmeczy Z, Vizi ES, Pacher P, Ledent C, Deitch EA, Spolarics Z, Németh ZH, Haskó G

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.

MeSH Terms
Adenosine A2 Receptor Agonists Animals CD3 Complex/immunology CD4 Antigens/immunology Cell Line Female Interferon-gamma/biosynthesis Interleukin-4/biosynthesis Lymphocyte Activation/genetics Male Mice Mice, Knockout RNA, Messenger/biosynthesis Receptor, Adenosine A2A/genetics,physiology Th1 Cells/immunology Th2 Cells/immunology
Chemicals
Adenosine A2 Receptor Agonists CD3 Complex CD4 Antigens RNA, Messenger Receptor, Adenosine A2A Interleukin-4 Interferon-gamma
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Csóka Balázs
Department of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Ave., University Heights, Newark, NJ 07103, USA.
Himer Leonóra
Selmeczy Zsolt
Vizi E Sylvester
Pacher Pál
Ledent Catherine
Deitch Edwin A
Spolarics Zoltán
Németh Zoltán H
Haskó György
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Article Info
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Abbr.
FASEB J
ISSN
1530-6860
DOI
10.1096/fj.08-107458
Published
2008-10-00
Epub
2008-00-14
Pages
3491-9
Language
English
Region
United States
NLM ID
8804484
PMCID
PMC2537430
Subset
IM
Grants
NIGMS NIH HHS · R01 GM066189-04 · United States
NIGMS NIH HHS · R01 GM066189-01 · United States
NIGMS NIH HHS · R01 GM66189 · United States
NIGMS NIH HHS · R01 GM066189-03 · United States
Intramural NIH HHS · United States
NIGMS NIH HHS · R01 GM066189 · United States
NCI NIH HHS · R01 CA163739 · United States
NIGMS NIH HHS · R01 GM066189-02 · United States
External Links
PubMed source DOI: 10.1096/fj.08-107458 PMC Full Text View journal details
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