Murine T lymphocytes modulate activity of an ATP-activated P2Z-type purinoceptor during differentiation.
Murine T, but not B, lymphocytes constitutively express a membrane receptor for adenosine nucleotides that opens a nonspecific pore that admits Ca2+ and ethidium (314 Da), but not propidium (415 Da) ions. ATP, ADP, and AMP show decreasing potency; UTP and adenosine are inactive. Nonhydrolyzable ATP analogues are completely ineffective. Oxidized ATP inhibits the response. Activity is detectable at ATP concentrations of 125 microM and peaks at 1 mM. The intracellular free Ca2+ ([Ca2+]i) rise is not reversed by removing ATP by centrifugation or apyrase. The kinetics, agonist and antagonist profiles, and the passage of ions as large as ethidium are the characteristics of a P2z-type purinoceptor. No expression of classical P2x-, P2u-, or P2Y-type purinoceptors can be detected. The [Ca2+]i elevating activity of the ATP receptor is modulated during T cell differentiation. CD4+8+ double-positive thymocytes are the least responsive. CD4-8+ single-positive thymocytes, CD8+ splenic T cells, CD4+8- single-positive thymocytes, and CD4+ splenic T cells show increasing reactivity. Measurement of P2Z expression by the rate of ethidium ion uptake correlates with the [Ca2+]i. The trimodal expression of P2Z by splenic CD4+ T cells correlates with the subsets defined by CD44 and CD45RB, differentiation Ags that distinguish memory cells: P2Zlow cells are CD44brightCD45RBbright; P2Zint are CD44dullCD45RBint; P2Zhigh are CD44brightCD45RBdull. It is suggested that P2Z receptor-mediated signaling could be involved in the regulation of differentiation and cell death in the thymus and peripheral T lymphocytes.
Chused
T M
TM
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.
Apasov
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S
Sitkovsky
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D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000502:physiology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D005260:Female; D016130:Immunophenotyping; D007424:Intracellular Fluid / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000494:pharmacology; D010084:Oxidation-Reduction; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D015398:Signal Transduction / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013498:Suramin / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology
D015220:Calcium Channels; D009711:Nucleotides; C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D013498:Suramin; D000255:Adenosine Triphosphate; D002118:Calcium