HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

OPEN ACCESS ARTICLE

This Article Free via Open Access: OA OA Full Text Full Text (PDF) OA All Versions of this Article: 2008.0111v1 26/7/1850    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 Grinnemo, K.-H. Articles by Corbascio, M. PubMed PubMed Citation Articles by Grinnemo, K.-H. Articles by Corbascio, M.

EMBRYONIC STEM CELLS

Costimulation Blockade Induces Tolerance to HESC Transplanted to the Testis and Induces Regulatory T-Cells to HESC Transplanted into the Heart

^aDepartment of Molecular Medicine and Surgery, Division of Cardiothoracic Surgery and Anesthesiology,
^bDepartment of Medicine, Division of Cardiology,
^cDepartment of Clinical Immunology, and
^dDepartment of Gynecology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden;
^eDepartment of Nephrology and Transplantation, Lund University, Lund, Sweden;
^fDepartment of Heart Diseases, Cardiothoracic Surgery, Haukelands University Hospital, Bergen, Norway

Key Words. Human embryonic stem cells • Foxp3⁺ T-cells • Tolerance • CTLA4Ig • anti-CD40L • anti-LFA-1

Correspondence: Karl-Henrik Grinnemo, M.D., Ph.D., Department of Molecular Medicine and Surgery, Division of Cardiothoracic Surgery and Anaesthesiology, Karolinska University Hospital, S-171 76, Stockholm, Sweden. Telephone: +46-8-51770000; Fax: +46-8-51773437; e-mail: karl-enrik.grinnemo{at}karolinska.se

Received February 4, 2008; accepted for publication April 15, 2008.
First published online in STEM CELLS EXPRESS   May 8, 2008.

In order to study the ability of costimulation blockade to induce tolerance to human embryonic stem cells (HESC), severe combined immunodeficient (SCID), and immunocompetent C57BL/6 mice treated with costimulation blockade received intratesticular and intramyocardial HESC transplants. All SCID mice with intratesticular HESC transplants developed teratoma. When SCID mice were transplanted intramyocardially, only two of five mice developed teratoma-like tumors. C57BL/6 mice transplanted intratesticularly and treated with costimulation blockade all developed teratoma and were surrounded by CD4⁺CD25⁺Foxp3⁺ T-cells, while isotype control treated recipients rejected their grafts. Most C57BL/6 mice transplanted intramyocardially and treated with costimulation blockade demonstrated lymphocytic infiltrates 1 month after transplantation, whereas one maintained its graft. Isolation of regulatory T-cells from intramyocardial transplanted recipients treated with costimulation blockade demonstrated specificity toward undifferentiated HESC and down-regulated naive T-cell activation toward HESC. These results demonstrate that costimulation blockade is sufficiently robust to induce tolerance to HESC in the immune-privileged environment of the testis. HESC specific regulatory T-cells developed to HESC transplanted to the heart and the success of transplantation was similar to that seen in SCID mice.

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