ArticleThe Journal of clinical investigation2000
Metabolites from apoptotic thymocytes inhibit thymopoiesis in adenosine deaminase-deficient fetal thymic organ cultures.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 38 citations in OpenAlex.
- Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients.Blood · 2008Trial
- Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy.Scientific reports · 2021Article
- Adenosine Deaminase Deficiency - More Than Just an Immunodeficiency.Frontiers in immunology · 2016Review
- Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Inborn errors of the development of human natural killer cells.Current opinion in allergy and clinical immunology · 2013Review
- Article
- Restoring balance to B cells in ADA deficiency.The Journal of clinical investigation · 2012Article
- Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID).Biologics : targets & therapy · 2009Article
- Restoration of adenosine deaminase-deficient human thymocyte development in vitro by inhibition of deoxynucleoside kinases.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Inhibition of deoxynucleoside kinases in human thymocytes prevents dATP accumulation and induction of apoptosis.Nucleosides, nucleotides & nucleic acids · 2008Article
- Further differentiation of murine double-positive thymocytes is inhibited in adenosine deaminase-deficient murine fetal thymic organ culture.Journal of immunology (Baltimore, Md. : 1950) · 2006Article
- polyethylene glycol-conjugated adenosine deaminase (ADA) therapy provides temporary immune reconstitution to a child with delayed-onset ADA deficiency.Clinical and diagnostic laboratory immunology · 2005Article
- Adenosine kinase inhibition promotes survival of fetal adenosine deaminase-deficient thymocytes by blocking dATP accumulation.The Journal of clinical investigation · 2002Article
- Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling.The Journal of clinical investigation · 2001Article
- Impaired thymopoiesis in interleukin-7 receptor transgenic mice is not corrected by Bcl-2.Cellular immunologyArticle
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Murine fetal thymic organ culture was used to investigate the mechanism by which adenosine deaminase (ADA) deficiency causes T-cell immunodeficiency. C57BL/6 fetal thymuses treated with the specific ADA inhibitor 2'-deoxycoformycin exhibited features of the human disease, including accumulation of dATP and inhibition of S-adenosylhomocysteine hydrolase enzyme activity. Although T-cell receptor (TCR) Vbeta gene rearrangements and pre-TCR-alpha expression were normal in ADA-deficient cultures, the production of alphabeta TCR(+) thymocytes was inhibited by 95%, and differentiation was blocked beginning at the time of beta selection. In contrast, the production of gammadelta TCR(+) thymocytes was unaffected. Similar results were obtained using fetal thymuses from ADA gene-targeted mice. Differentiation and proliferation were preserved by the introduction of a bcl-2 transgene or disruption of the gene encoding apoptotic protease activating factor-1. The pan-caspase inhibitor carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone also significantly lessened the effects of ADA deficiency and prevented the accumulation of dATP. Thus, ADA substrates accumulate and disrupt thymocyte development in ADA deficiency. These substrates derive from thymocytes that undergo apoptosis as a consequence of failing to pass developmental checkpoints, such as beta selection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.