title: Influence of adenosine deaminase inhibition on the phosphoinositide turnover in the initial stages of human T cell activation.
abstract: An experimental model of adenosine deaminase deficiency was established on the human T cell line Jurkat by using 2'-deoxycoformycin, a strong specific inhibitor of the enzyme. When deoxyadenosine was added to the inhibited cells, the nucleotide profile was modified reproducing that found in lymphocytes from adenosine deaminase-deficient children. The metabolism of phosphoinositides, analyzed by either the release of [3H]inositol phosphates or the breakdown of 32P-prelabeled phosphatidyl inositides, was compared in normal and modified cells where dATP was accumulated. No modification in 32P labeling of phosphoinositides was detectable within the 32P-loading period. However, when the cells were stimulated by phytohemagglutinin or anti-CD3 monoclonal antibody, the phosphoinositide hydrolysis was strongly reduced in the dATP-containing lymphoblasts. This decrease was correlated with the intracellular dATP concentration.
authors.affiliation: Faculté de Médecine, Necker-Enfants Malades, INSERM U75, Paris, France.
authors.forename: H A
authors.initials: HA
authors.lastname: Buc
authors.forename: A
authors.initials: A
authors.lastname: Moncion
authors.forename: M
authors.initials: M
authors.lastname: Hamet
authors.forename: A M
authors.initials: AM
authors.lastname: Houllier
authors.forename: L
authors.initials: L
authors.lastname: Thuilier
authors.forename: J L
authors.initials: JL
authors.lastname: Perignon
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency; D058892:Adenosine Deaminase Inhibitors; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002460:Cell Line; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003838:Deoxyadenine Nucleotides; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D015649:Pentostatin; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; C026600:2'-deoxyadenosine triphosphate