Activation of the adenosine A2A receptor attenuates experimental autoimmune myasthenia gravis severity

Eur J Immunol. 2012 May;42(5):1140-51. doi: 10.1002/eji.201142088.


The adenosine A2A receptor (A2AR) is the major cellular adenosine receptor commonly associated with immunosuppression. Here, we investigated whether A2AR activation holds the potential for impacting the severity of experimental autoimmune myasthenia gravis (EAMG) induced following immunization of Lewis rats with the acetylcholine receptor (AChR) R97-116 peptide. This report demonstrates reduced A2AR expression by both T cells and B cells residing in spleen and lymph nodes following EAMG induction. A2AR stimulation inhibited anti-AChR antibody production and proliferation of AChR-specific lymphocytes in vitro. Inhibition was blocked with the A2AR antagonists or protein kinase A inhibitor. We also determined that the development of EAMG was accompanied by a T-helper cell imbalance that could be restored following A2AR stimulation that resulted in increased Treg cell levels and a reduction in Th1-, Th2-, and Th17-cell subtypes. An EAMG-preventive treatment regimen was established that consisted of (2-(p-(2-carbonylethyl)phenylethylamino)-5-N-ethylcarboxamidoadenosine) (CGS21680; A2AR agonist) administration 1 day prior to EAMG induction. Administration of CGS21680 29 days post EAMG induction (therapeutic treatment) also ameliorated disease severity. We conclude that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of myasthenia gravis or other T-cell- and B-cell-mediated autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / administration & dosage
  • Adenosine / analogs & derivatives*
  • Adenosine / therapeutic use
  • Adenosine A2 Receptor Agonists / administration & dosage
  • Adenosine A2 Receptor Agonists / therapeutic use*
  • Adenosine A2 Receptor Antagonists / pharmacology
  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Female
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Myasthenia Gravis, Autoimmune, Experimental / drug therapy*
  • Myasthenia Gravis, Autoimmune, Experimental / immunology*
  • Phenethylamines / administration & dosage
  • Phenethylamines / therapeutic use*
  • Rats
  • Rats, Inbred Lew
  • Receptor, Adenosine A2A / metabolism*
  • Receptors, Cholinergic / immunology
  • Severity of Illness Index
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology


  • Adenosine A2 Receptor Agonists
  • Adenosine A2 Receptor Antagonists
  • Antibodies, Neutralizing
  • Phenethylamines
  • Receptor, Adenosine A2A
  • Receptors, Cholinergic
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Adenosine