THE INVOLVEMENT OF AN ATP-GATED ION-CHANNEL, P-2X1, IN THYMOCYTE APOPTOSIS

In the immune system, apoptosis is involved in intrathymic elimination of self-reactive thymocytes and in peripheral T cell tolerance to exo genous antigens. Here, we describe the role in T cell apoptosis of P-2 x1, a nonselective cation channel activated by ATP. P-2x1 molecules ar e up-regulated in thymocytes during dexamethasone-induced apoptosis, a nd antagonists to these receptors protect thymocytes from cell death. Moreover, P-2x1 mRNA and protein levels increase in thymocytes induced to die in vivo by the superantigen staphylococcal enterotoxin B. In c ontrast, T cells undergoing apoptosis in the periphery do not express P-2x1. The demonstration that P-2x1 ion channels play a role in the ap optosis of thymocytes but not peripheral T cells illustrates a novel m echanism contributing to thymocyte cell death and opens new possibilit ies for investigating clonal deletion in the thymus.