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This Article Free via Open Access: OA OA Full Text Full Text (PDF) Supplemental Data OA All Versions of this Article: 2008-0078v1 26/8/1939    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Google Scholar Articles by Wu, D. C. Articles by Wood, K. J. PubMed PubMed Citation Articles by Wu, D. C. Articles by Wood, K. J.

EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS

Embryonic Stem Cells and Their Differentiated Derivatives Have a Fragile Immune Privilege but Still Represent Novel Targets of Immune Attack

Transplantation Research Immunology Group, Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom

Key Words. Cell transplantation • Embryonic stem cells • Immune escape • Immunobiology • Differentiation

Correspondence: Kathryn J. Wood, D.Phil., Transplantation Research Immunology Group, Nuffield Department of Surgery, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. Telephone: 00-44-(0)-1865-222508; Fax: 00-44-(0)-1865-768876; e-mail: kathryn.wood{at}nds.ox.ac.uk

Received February 27, 2008; accepted for publication April 30, 2008.
First published online in STEM CELLS EXPRESS   June 5, 2008.

Embryonic stem cells (ESCs) offer an attractive potential in cell replacement therapy and regenerative medicine because of their inherent plasticity and ability to self-renew. However, the immunological response against transplanted ESC-derived allografts requires further evaluation. In this study, we showed that ESCs expressing the major histocompatibility complex class I molecule H2K^b escape immune recognition by H2K^b-reactive CD8⁺ T cells, irrespective of H2K^b expression levels. In the face of more robust immunological challenge, however, evidence of ESC allograft rejection becomes apparent. We further assessed the adaptive immune response against terminally differentiated insulin-producing tissue derived from an ESC source to examine the potential future applicability of this tissue as a β-cell replacement therapy for type 1 diabetes mellitus. The functional ESC-derived insulin-producing tissue was infiltrated by alloreactive T cells and rejected in immunocompetent hosts. Hence, although ESCs and their terminally differentiated derivatives may possess a fragile immune privilege, they still represent novel targets of attack by elements of the immune system and are rejected. These findings provide insight into the mechanisms of adaptive immunity toward ESCs and their derivatives.

Disclosure of potential conflicts of interest is found at the end of this article.