ArticleThe Journal of clinical investigation2020
Ecto-NTPDase CD39 is a negative checkpoint that inhibits follicular helper cell generation.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 34 citations in OpenAlex.
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- Adenosine deaminase co-immunization reverses age-associated immunosenescence by restoring germinal center T follicular helper cell function.bioRxiv : the preprint server for biology · 2026Article
- The CD39-CD73-adenosine axis: a pivotal regulator of retinal homeostasis and diseases.Frontiers in cell and developmental biology · 2026Review
- T follicular helper cell development during malaria.Current opinion in immunology · 2025Review
- Adenosine metabolism and receptors in aging of the skin, musculoskeletal, immune and cardiovascular systems.Ageing research reviews · 2025Review
- Metabolic Signaling as a Driver of T Cell Aging.Immune network · 2025Review
- GzmkFrontiers in immunology · 2025Review
- CD39 is an antibody-secreting B-cell marker that modulates germinal center and antibody responses during infection.Frontiers in immunology · 2025Article
- SNP rs10748643 determines CD39 expression in T and NK cells through altering NFIC binding affinity rather than interfering with RNA splicing.Frontiers in immunology · 2025Article
- T Cell Aging: An Important Target for Perioperative Immunomodulation.Clinical interventions in aging · 2025Review
- Heterologous expression and biochemical characterization of the recombinant nucleoside triphosphate diphosphohydrolase 2 (LbNTPDase2) from Leishmania (Viannia) braziliensis.Purinergic signalling · 2024Article
- The aged microenvironment impairs BCL6 and CD40L induction in CD4Aging cell · 2024Article
- Help me help you: emerging concepts in T follicular helper cell differentiation, identity, and function.Current opinion in immunology · 2024Review
- Hypoxia-adenosinergic regulation of B cell responses.Frontiers in immunology · 2024Review
- Article
- T cell fate decisions during memory cell generation with aging.Seminars in immunology · 2023Review
- The interplay between the DNA damage response and ectonucleotidases modulates tumor response to therapy.Science immunology · 2023Review
- T cell aging and Alzheimer's disease.Frontiers in immunology · 2023Review
- Article
- T-Cell Aging-Associated Phenotypes in Autoimmune Disease.Frontiers in aging · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Vaccination is a mainstay in preventive medicine, reducing morbidity and mortality from infection, largely by generating pathogen-specific neutralizing antibodies. However, standard immunization strategies are insufficient with increasing age due to immunological impediments, including defects in T follicular helper (Tfh) cells. Here, we found that Tfh generation is inversely linked to the expression of the ecto-NTPDase CD39 that modifies purinergic signaling. The lineage-determining transcription factor BCL6 inhibited CD39 expression, while increased Tfh frequencies were found in individuals with a germline polymorphism preventing transcription of ENTPD1, encoding CD39. In in vitro human and in vivo mouse studies, Tfh generation and germinal center responses were enhanced by reducing CD39 expression through the inhibition of the cAMP/PKA/p-CREB pathway, or by blocking adenosine signaling downstream of CD39 using the selective adenosine A2a receptor antagonist istradefylline. Thus, purinergic signaling in differentiating T cells can be targeted to improve vaccine responses, in particular in older individuals who have increased CD39 expression.
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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.