Extracellular adenosine regulates naive T cell development and peripheral maintenance

Caglar Cekic, Duygu Sag, Yuan Ji Day, Joel Linden*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

81 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)2693-2706
Number of pages14
JournalJournal of Experimental Medicine
Volume210
Issue number12
DOIs
StatePublished - 11 2013

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