EFFECTS OF EXTRACELLULAR ATP AND ADENOSINE ON DIFFERENT THYMOCYTE SUBSETS - POSSIBLE ROLE OF ATP-GATED CHANNELS AND C-PROTEIN-COUPLED PURINERGIC RECEPTOR

To explore the possible role of purinergic receptors in thymocyte deve lopment and in pathogenesis of adenosine deaminase SCID, we studied ef fects of extracellular adenosine triphosphate (ATP(ext)) and adenosine on TCR- and steroid hormone-triggered processes in mouse thymocytes. Reverse transcriptase-PCR analysis confirms the mRNA expression of sev eral types of purinergic receptors, while the functioning of ATP recep tors in thymocytes is reflected by ATP(ext)-induced intracellular calc ium increases and by thymocyte subset-specific sensitivity to the effe cts of ATP(ext) and adenosine, Only ATP(ext), but not the ATP cataboli tes, adenosine, dexamethasone, or TCR cross-linking, was efficient in triggering rapid protein synthesis independent lysis of CD4(+)8(-) thy mocytes and peripheral CD4(+) T cells, In contrast, extracellular aden osine specifically induced the apoptosis of CD4(+)8(+) thymocytes, ATP (ext) also induced a slower process of DNA fragmentation and protein s ynthesis-dependent apoptosis in all thymocyte subsets, ATP(ext) had an additive effect with TCR cross-linking in the induction of thymocyte death, but, unexpectedly, the effects of ATP(ext) at high concentratio n were antagonistic to steroid-induced apoptosis, Described here, the properties of ATP(ext) and adenosine are consistent with their involve ment in the regulation of T cell development due to differential expre ssion and signaling through purinergic receptors in different thymocyt e subsets, The possible role of purinergic receptor signaling in T cel l differentiation and adenosine deaminase SCID is discussed.