Extracellular adenosine regulates naive T cell development and peripheral maintenance

Area of Science:

• Immunology
• Cell Biology

Background:

• Adenosine, a metabolic byproduct, suppresses T cell receptor (TCR) signaling.
• Naive T cell maintenance relies on environmental sensors that inhibit TCR signals, but these are not fully identified.

Purpose of the Study:

• To investigate the role of the adenosine A2A receptor (A2AR) in T cell development and naive T cell maintenance.

Main Methods:

• Generated mice with a floxed adenosine A2A receptor (A2AR) gene (Adora2a).
• Performed global and T cell-specific A2AR deletion studies.
• Analyzed T cell populations, TCR signaling pathways (PI3K-AKT), and IL-7Rα expression in wild-type and knockout mice, including chimeric models.

Main Results:

• A2AR deletion led to a decrease in naive T cells, but not memory T cells.
• A2AR signaling maintains naive T cells by inhibiting TCR-induced PI3K-AKT activation, reducing IL-7Rα downregulation and apoptosis.
• A2AR deletion resulted in decreased IL-7Rα expression in naive T cells, a cell-intrinsic effect.
• A2AR expression is upregulated during thymic T cell development, aiding progression and IL-7Rα expression.

Conclusions:

• A2AR signaling is essential for regulating T cell development in the thymus.
• A2AR signaling maintains peripheral naive T cell populations by controlling quiescence and survival.
• A2AR acts as a critical environmental sensor for naive T cell homeostasis.