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

Cell Transplantation

Article

Jochen Seissler¹  Manuela Steinsdoerfer¹  Christine Sattler¹  Monika Offers¹  Rudolf Schierl²  Elke Fischer²  Kathrin Heseler³  Walter Däubener³ 

[1] Diabetes Center, Medical Clinic-Innenstadt, Ludwig-Maximilians-University, Munich, Germany;Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Munich, Germany;Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University, Duesseldorf, Germany;

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

DOI  :  10.3727/096368910X546553

 received in 2010-07-12, accepted in 2010-11-23,  发布年份 2011

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2011 Cognizant Comm. Corp.

【 图 表 】

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