MODULATION OF T CELL FUNCTION BY ATP, ADENOSINE, AND P1/P2 RECEPTORS

Abstract

Trauma affects T cell function, which can result in immunosuppression and sepsis. Tissue damage in trauma patients can increase extracellular ATP and adenosine concentrations. Here we examined how ATP and adenosine influence T cell function. Using Real-Time RT-PCR, we found that human CD4+T cells and Jurkat T cells express similar patterns of multiple P1 adenosine and P2 ATP receptor subtypes. T cells predominantly express A2A adenosine receptors and the P2X4 and P2X5 nucleotide receptor subtypes, and moderate to low levels of P2X1, and other nucleotide receptors. Cell stimulation with phytohemagglutinin (PHA; 50 ng/ml) and phorbol ester (PMA; 5 ng/ml) increased P2X1 and P2X5 receptor mRNA and protein expression, suggesting that stimulated cells are more susceptible to exogenous ATP. We found that ATP and adenosine elicit opposing actions on interleukin-2 (IL-2) mRNA induction and IL-2 expression of activated T cells. We found that P2 receptor activation with ATP or with the non-hydrolysable ATP analog ATPγS enhanced IL-2 expression. In contrast, P1 adenosine receptor stimulation with adenosine or with A2A receptor agonists suppressed IL-2 expression. These results suggest that ATP and its product adenosine regulate T cell activation by positive feedback through P2 receptor activation and by a negative feedback loop that involves A2A receptor activation. The relevant receptors may represent possible therapeutic targets to modulate T cell responses in trauma patients. Supported in part by grants from USAMRMC and NIGMS.