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Weiler, M.* ; Schmetzer, H. ; Braeu, M. ; Buhmann, R.

Inhibitory effect of extracellular purine nucleotide and nucleoside concentrations on T cell proliferation.

Exp. Cell Res. 349, 1-14 (2016)
Postprint DOI PMC
Open Access Green
The release of nucleic acids and derivatives after tissue-injury may affect cellular immune-response. We studied the impact of extracellular ribo-, desoxyribonucleotides and nucleosides on T-cell immunity. Peripheral-blood-mononuclear-cells (PBMCs) or isolated CD3(+)T-cells obtained from 6 healthy donors were stimulated via CD3/CD28 Dynabeads or dendritic cells (DCs) in the presence or absence of pyrimidine-, purine-nucleotides and -nucleosides (range 2-200µM). Addition of deoxy-, guanosine-triphosphate (dGTP, GTP) and guanosine resulted in a partial inhibition of the induced T-cell-proliferation. Adenosine-triphosphate (ATP), adenosine and the pyrimidine-ribo- and -deoxyribonucleotides displayed no inhibitory capacity. Inhibitory effects of dGTP and GTP, but not of guanosine and ATP were culture-media-dependent and could be almost abrogated by use of lymphocyte-culture-media Xvivo15 instead of RPMI with standard-supplementation. In contrast to RPMI, Xvivo15 resulted in a significant down-regulation of the cell-surface-located ectonucleotidases CD39 (Ecto-Apyrase) and CD73 (Ecto-5´-Nucleotidase), critical for the extracellular nucleotides-hydrolysis to nucleosides, explaining the loss of inhibition mediated by dGTP and GTP, but not Guanosine. In line with previous findings ATP was found to exert immunosuppressive effects on T-cell-proliferation. Purine-nucleotides, dGTP and GTP displayed a higher inhibitory capacity, but seem to be strictly dependent on the microenvironmental conditions modulating the responsiveness of the respective T-lymphocytes. Further evaluation of experimental and respective clinical settings should anticipate these findings.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords T Cell Proliferation ; Extracellular Milieu ; Nucleosides ; Nucleotides; Human-lymphocyte Function; In-vitro; Dendritic Cells; Culture-media; Deoxyguanosine; Depletion; Toxicity; Guanosine; Leukemia; Blood
ISSN (print) / ISBN 1090-2422
e-ISSN 0014-4827
Journal Experimental Cell Research
Quellenangaben Volume: 349, Issue: 1, Pages: 1-14 Article Number: , Supplement: ,
Publisher Academic Press
Publishing Place Orlando, Fla.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Immunotherapy (KKG-KIT)