Immunosuppression By Embryonic Stem Cells

¹ Transplantation Biology Program and the Departments of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
² Transplantation Biology Program and the Departments of Immunology, Surgery and Pediatrics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

^* To whom correspondence should be addressed. E-mail: platt.jeffrey{at}mayo.edu.

	Abstract

Embryonic stem cells or their progeny inevitably differ genetically from those who might receive the cells as transplants. We tested the barriers to engraftment of embryonic stem cells and the mechanisms that determine those barriers. Using formation of teratomas as a measure of engraftment, we found that semi-allogeneic and fully allogeneic embryonic stem cells engraft successfully in mice, provided a sufficient number of cells is delivered. Successfully engrafted cells did not generate immunological memory; unsuccessfully engrafted cells did. Embryonic stem cells reversibly, and in a dose-dependant manner, inhibited T cell proliferation to various stimuli and the maturation of antigen presenting cells induced by lipopolysaccharide. Inhibition of both was owed at least in part to production of TGF- by the embryon ic stem cells. Thus, murine embryonic stem cells exert "immunosuppression" locally, enabling engraftment across allogeneic barriers.

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