title: Inhibition of T-cell proliferation by murine multipotent mesenchymal stromal cells is mediated by CD39 expression and adenosine generation.
abstract: Multipotent mesenchymal stromal cells (MSCs) are bone marrow-derived cells of nonhematopoietic origin with immunoregulatory properties. Although some functions of MSCs have been identified, there are still features that are not explained thus far. The aim of the present study was to  identify novel factors involved in MSC-mediated inhibition of T-cell proliferation. We here demonstrate that the surface molecule CD39 is coexpressed in concert with CD73 on murine MSCs catalyzing the generation of adenosine, which can directly act on activated T cells via the adenosine A2A  receptor. Blocking of the adenosine pathway either by the A2A receptor antagonist SCH58261 or the specific CD39 inhibitor polyoxotungstate 1 (POM-1) blocked MSC-mediated suppression of T-cell proliferation almost completely. We conclude that CD39/CD73 coexpression is a novel important component  of the immunoregulatory functions of murine MSCs. Our findings may both be important to improve our understanding of MSC function and for the development of immunomodulatory cellular therapies.
authors.affiliation: Diabetes Center, Medical Clinic-Innenstadt, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Sattler
authors.forename: Manuela
authors.initials: M
authors.lastname: Steinsdoerfer
authors.forename: Monika
authors.initials: M
authors.lastname: Offers
authors.forename: Elke
authors.initials: E
authors.lastname: Fischer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schierl
authors.forename: Kathrin
authors.initials: K
authors.lastname: Heseler
authors.forename: Walter
authors.initials: W
authors.lastname: Däubener
authors.forename: Jochen
authors.initials: J
authors.lastname: Seissler
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000096:biosynthesis*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008934:Mitogens; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine