The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Human CD4+CD39+ regulatory T cells produce adenosine upon co-expression of surface CD73 or contact with CD73+ exosomes or CD73+ cells
Open accessAbstract
Summary: While murine CD4+CD39+ regulatory T cells (Treg) co-express CD73 and hydrolyze exogenous (e) adenosine triphosphate (ATP) to immunosuppressive adenosine (ADO), surface co-expression of CD73 on human circulating CD4+CD39+Treg is rare. Therefore, the ability of human Treg to produce and utilize ADO for suppression remains unclear. Using mass spectrometry, we measured nucleoside production by subsets of human CD4+CD39+ and CD4+CD39(–)CD73+T cells or CD19+B cells isolated from blood of 30 volunteers and 14 cancer patients. CD39 and CD73 expression was evaluated by flow cytometry, Western blots, confocal microscopy or reverse transcription–polymerase chain reaction (RT–PCR). Circulating CD4+CD39+Treg which hydrolyzed eATP to 5′-AMP contained few intracytoplasmic granules and had low CD73 mRNA levels. Only ∼1% of these Treg were CD39+CD73+. In contrast, CD4+CD39negCD73+T cells contained numerous CD73+ granules in the cytoplasm and strongly expressed surface CD73. In vitro-generated Treg (Tr1) and most B cells were CD39+CD73+. All these CD73+T cell subsets and B cells hydrolyzed 5′-AMP to ADO. Exosomes isolated from plasma of normal control (NC) or cancer patients carried enzymatically active CD39 and CD73+ and, when supplied with eATP, hydrolyzed it to ADO. Only CD4+CD39+Treg co-incubated with CD4+CD73+T cells, B cells or CD39+CD73+ exosomes produced ADO. Thus, contact with membrane-tethered CD73 was sufficient for ADO production by CD4+CD39+Treg. In microenvironments containing CD4+CD73+T cells, B cells or CD39+CD73+ exosomes, CD73 is readily available to CD4+CD39+CD73negTreg for the production of immunosuppressive ADO.
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Immunity, inflammation and cancer: a leading role for adenosine
Antonioli, L., Blandizzi, C., Pacher, P., & Haskó, G. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3613 · Cited by 765
Adenosine, an endogenous distress signal, modulates tissue damage and repair
Fredholm, B. B. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402132 · Cited by 686
Regulatory T cells: recommendations to simplify the nomenclature
Abbas, A. K., Benoist, C., Bluestone, J. A., Campbell, D. J., Ghosh, S., Hori, S., Jiang, S., Kuchroo, V. K., Mathis, D., Roncarolo, M. G., et al. (2013) · Nature Immunology · doi:10.1038/ni.2554 · Cited by 623
Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis
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Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production
Clayton, A., Al-Taei, S., Webber, J., Mason, M. D., & Tabi, Z. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003884 · Cited by 540
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The ectonucleotidases CD 39 and CD 73: Novel checkpoint inhibitor targets
Allard, B., Longhi, M. S., Robson, S. C., & Stagg, J. (2017) · Immunological Reviews · doi:10.1111/imr.12528 · Cited by 927
Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy
Tay, C., Tanaka, A., & Sakaguchi, S. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.014 · Cited by 580
Immunosuppressive Activities of Adenosine in Cancer
Allard, B., Beavis, P. A., Darcy, P. K., & Stagg, J. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.04.001 · Cited by 292
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Vignali, P. D. A., DePeaux, K., Watson, M. J., Ye, C., Ford, B. R., Lontos, K., McGaa, N. K., Scharping, N. E., Menk, A. V., Robson, S. C., et al. (2023) · Nature Immunology · doi:10.1038/s41590-022-01379-9 · Cited by 269
Metadata
- Authors
- Schuler, P. J., Saze, Z., Hong, C.-S., Muller, L., Gillespie, D. G., Cheng, D., Harasymczuk, M., Mandapathil, M., Lang, S., Jackson, E. K., & Whiteside, T. L.
- Venue
- Clinical and Experimental Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-07-09
- Volume
- 177
- Issue
- 2
- Pages
- 531-543
- ISSN
- 0009-9104 (ISSN-L)
- 1365-2249
- OpenAlex
- W1705652018
- Cited by
- 277
- References
- 41
- FWCI
- 12.32
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Human CD4+CD39+ regulatory T cells produce adenosine upon co-expression of surface CD73 or contact with CD73+ exosomes or CD73+ cells. https://app.cochat.ai/papers/10.1111/cei.12354
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- Schuler, P. J., Saze, Z., Hong, C.-S., Muller, L., Gillespie, D. G., Cheng, D., Harasymczuk, M., Mandapathil, M., Lang, S., Jackson, E. K., & Whiteside, T. L. (2014). Human CD4+CD39+ regulatory T cells produce adenosine upon co-expression of surface CD73 or contact with CD73+ exosomes or CD73+ cells. Clinical and Experimental Immunology. https://doi.org/10.1111/cei.12354
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