title: Effects of extracellular ATP and adenosine on different thymocyte subsets: possible role of ATP-gated channels and G protein-coupled purinergic receptor.
abstract: To explore the possible role of purinergic receptors in thymocyte development and in pathogenesis of adenosine deaminase SCID, we studied effects 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 several types of purinergic receptors, while the functioning of ATP receptors in thymocytes is reflected by ATP(ext)-induced intracellular calcium increases and by thymocyte subset-specific sensitivity to the effects of ATP(ext) and adenosine. Only ATP(ext), but not the ATP catabolites, adenosine, dexamethasone, or TCR cross-linking, was efficient in triggering rapid protein synthesis independent lysis of CD4+8- thymocytes and peripheral CD4+ T cells. In contrast, extracellular adenosine specifically induced the apoptosis of CD4+8+ thymocytes. ATP(ext) also induced a slower process of DNA fragmentation and protein synthesis-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 concentration were antagonistic to steroid-induced apoptosis. Described here, the properties of ATP(ext) and adenosine are consistent with their involvement in the regulation of T cell development due to differential expression and signaling through purinergic receptors in different thymocyte subsets. The possible role of purinergic receptor signaling in T cell differentiation and adenosine deaminase SCID is discussed.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Apasov
authors.forename: M
authors.initials: M
authors.lastname: Koshiba
authors.forename: T M
authors.initials: TM
authors.lastname: Chused
authors.forename: M V
authors.initials: MV
authors.lastname: Sitkovsky
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000276:immunology; D015640:Ion Channel Gating; D007473:Ion Channels / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000276:immunology; D011983:Receptors, Purinergic / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*
chemical_list: D007473:Ion Channels; D011971:Receptors, Immunologic; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D000241:Adenosine