ArticleThe Journal of clinical investigation2002
Adenosine kinase inhibition promotes survival of fetal adenosine deaminase-deficient thymocytes by blocking dATP accumulation.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients.Blood · 2008Trial
- Inborn errors of immunity associated with defects of thymic development.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2022Review
- Nonconditioned ADA-SCID gene therapy reveals ADA requirement in the hematopoietic system and clonal dominance of vector-marked clones.Molecular therapy. Methods & clinical development · 2021Article
- Toll-like receptor signaling in primary immune deficiencies.Annals of the New York Academy of Sciences · 2015Review
- Adenosine deaminase deficient severe combined immunodeficiency presenting as atypical haemolytic uraemic syndrome.Journal of clinical immunology · 2015Article
- Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension.Mediators of inflammation · 2015Article
- A role for apoptosis-inducing factor in T cell development.The Journal of experimental medicine · 2012Article
- CD73-generated adenosine promotes osteoblast differentiation.Journal of cellular physiology · 2012Article
- Primary immunodeficiency diseases associated with neurologic manifestations.Journal of clinical immunology · 2012Review
- Adenosine deaminase deficiency: unanticipated benefits from the study of a rare immunodeficiency.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Autoimmune dysregulation and purine metabolism in adenosine deaminase deficiency.Frontiers in immunology · 2012Article
- PRPS1 mutations: four distinct syndromes and potential treatment.American journal of human genetics · 2010Review
- 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
- CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Article
- 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
- 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
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Thymocyte development past the CD4(-)CD8(-) stage is markedly inhibited in adenosine deaminase-deficient (ADA-deficient) murine fetal thymic organ cultures (FTOCs) due to the accumulation of ADA substrates derived from thymocytes failing developmental checkpoints. Such cultures can be rescued by overexpression of Bcl-2, suggesting that apoptosis is an important component of the mechanism by which ADA deficiency impairs thymocyte development. Consistent with this conclusion, ADA-deficient FTOCs were partially rescued by a rearranged T cell receptor beta transgene that permits virtually all thymocytes to pass the beta-selection checkpoint. ADA-deficient cultures were also rescued by the adenosine kinase inhibitor 5'-amino-5'-deoxyadenosine (5'A5'dAdo), indicating that the metabolite responsible for the inhibition of thymocyte development is not adenosine or deoxyadenosine, but a phosphorylated derivative of an ADA substrate. Correction of ADA-deficient FTOCs by 5'A5'dAdo correlated with reduced accumulation of dATP, implicating this compound as the toxic metabolite. In ADA-inhibited FTOCs rescued with a Bcl-2 transgene, however, dATP levels were superelevated, suggesting that cells failing positive and negative selection continued to contribute to the accumulation of ADA substrates. Our data are consistent with dATP-induced mitochondrial cytochrome c release followed by apoptosis as the mechanism by which ADA deficiency leads to reduced thymic T cell production.
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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.