Extracellular adenosine regulates naive T cell development and peripheral maintenance.

摘要: Adenosine produced as a byproduct of metabolic activity is present in all tissues and produces dose-dependent suppression TCR signaling. Naive T cell maintenance depends on inhibition signals by environmental sensors, which are yet to be fully defined. We mice with floxed adenosine A2A receptor (A2AR) gene, Adora2a, show that either global A2AR deletion or cre-mediated elicits decline the number naive but not memory cells. signaling maintains cells quiescent state inhibiting TCR-induced activation phosphatidylinositide 3-kinase (PI3K)-AKT pathway, thereby reducing IL-7Rα down-regulation apoptosis. Patterns expression chimeric reconstituted Adora2a(+/+) Adora2a(-/-) bone marrow suggest decreased cell-intrinsic consequence Adora2a deletion. In addition, increases early thymic development contributes progression double-negative precursors single-positive thymocytes increased expression. Therefore, regulates sustain normal numbers periphery.