P2X7 receptor expression levels determine lethal effects of a purine based danger signal in T lymphocytes

Contact of T lymphocytes with nicotinamide adenine dinucleotide (NAD) or ATP causes cell death that requires expression of purinergic receptor P2X7 (P2X7R). T cell subsets differ in their responses to NAD and ATP, which awaits a mechanistic explanation. Here, we show that sensitivity to ATP correlates with P2X7R expression levels in CD4 cells, CD8 cells and CD4+CD25+ cells from both C57BL/6 and BALB/c mice. But P2X7R ligands do not only induce cell death but also shedding of CD62L. It is shown here that in CD62Lhigh T cells, CD62L shedding correlates with low expression of P2X7Rs and lower cell death, whereas in CD62Llow cells P2X7R expression and death are higher. The possibility is therefore investigated that P2X7Rs induce T cell activation. Experiments show that spontaneous T cell proliferation is somewhat higher in cells expressing P2X7Rs, but this effect we suggest is caused by P2X7R expression on accessory cells.