Adenosine and anergy

T cells must integrate multiple environmental cues when deciding whether to mount an immunogenic or tolerogenic response. Since not all self-reactive T cells are eliminated during thymic development, mechanisms of peripheral tolerance such as T cell anergy contribute to preventing autoimmunity. Recent studies have implicated extracellular adenosine and the adenosine A_2A receptor as playing an important role in inhibiting T cell effector function. Herein, we review the current literature regarding T cell anergy and the emerging literature implicating the A_2A receptor as critical regulator of immune activation. Finally, we present evidence to suggest a possible role for adenosine A_2A receptor signaling in T cell anergy.