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Stem Cells 2003;21:405-416 www.StemCells.com
© 2003 AlphaMed Press

Neural Progenitor Cells Lack Immunogenicity and Resist Destruction as Allografts

Junko Horia,b, Tat Fong Nga, Marie Shatosa, Henry Klassenc, J. Wayne Streileina, Michael J. Younga

a Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA
b Department of Ophthalmology, Nippon Medical School, Tokyo, Japan
c Stem Cell Research, Children’s Hospital of Orange County, Orange, California, USA

Key Words. Stem cells • Transplantation • MHC • Tolerance • Suppression • Anergy • Neural

Michael J. Young, Ph.D., Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts, USA 02114. Telephone: 617-912-7419; Fax: 617-912-0101; e-mail: mikey{at}vision.eri.harvard.edu

Multipotent, self-renewing stem and progenitor cells isolated from the mammalian central nervous system (CNS) have been shown to survive as allografts following transplantation to sites throughout the neuraxis. However, studies of this type shed little light upon the immunologic properties of the cells themselves, primarily because little is learned about the intrinsic immunogenic properties of a cell when it is grafted into an immune-privileged site. We have therefore investigated the immunogenic and antigenic properties of CNS progenitor cells by grafting them into a conventional (i.e., non-immune-privileged) site, namely, beneath the kidney capsule. Our results indicate that allogeneic CNS progenitor cells survive at least 4 weeks in a conventional site, during which time they neither sensitize their hosts nor express detectable levels of major histocompatibility complex (MHC) class I or II. These in vivo data are in accord with flow cytometric results showing that CNS progenitor cells do not express MHC class I or class II, either at baseline or upon differentiation in 10% serum. Exposure to interferon gamma, however, reversibly upregulates expression of these key transplantation antigens. Together, these results reveal CNS progenitor cells to possess inherent immune privilege. Since CNS progenitor cell allografts were rejected beneath the kidney capsule following specific sensitization of the host, CNS progenitor cells were able to display alloantigens, albeit not in an immunogenic form.




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