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Open Access Inhibition of T-Cell Proliferation by Murine Multipotent Mesenchymal Stromal Cells Is Mediated by CD39 Expression and Adenosine Generation

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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.

Keywords: Adenosine; CD39/CD73; Immunoregulation; Mesenchymal stromal cells (MSCs); T-cell inhibition

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368910X546553

Publication date: August 1, 2011

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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