A Role for Regulatory T Cells in Acceptance of ESC‐Derived Tissues Transplanted Across an Major Histocompatibility Complex Barrier

We have previously reported that ESC‐derived tissues are subject to some level of immune privilege, which might facilitate induction of immune tolerance. Herein, we further demonstrate that fully allogeneic ESC‐derived tissues are accepted with a regimen of coreceptor blockade even in recipients kno...

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Published inStem cells (Dayton, Ohio) Vol. 28; no. 10; pp. 1905 - 1914
Main Authors Lui, Kathy O., Boyd, Ashleigh S., Cobbold, Stephen P., Waldmann, Herman, Fairchild, Paul J.
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2010
Subjects
Animals
CD8-Positive T-Lymphocytes - immunology
Cell Line
Embryonic Stem Cells - cytology
ESC
Female
Immune privilege
Immunohistochemistry
Major Histocompatibility Complex - immunology
Male
MHC
Mice
Mice, Inbred C57BL
Polymerase Chain Reaction
Regulatory T cells
Stem cell
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
Transplantation
Transplantation Tolerance - immunology
Transplantation, Homologous - immunology
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Summary:We have previously reported that ESC‐derived tissues are subject to some level of immune privilege, which might facilitate induction of immune tolerance. Herein, we further demonstrate that fully allogeneic ESC‐derived tissues are accepted with a regimen of coreceptor blockade even in recipients known to be relatively resistant to such a tolerizing protocol. Moreover, ESC‐derived tissues could be spontaneously accepted across a class I major histocompatibility complex disparity. We further show that CD4+FoxP3+ regulatory T cells (Treg) appear to be essential for this natural “privileged” state as their ablation with an anti‐CD25 mAb results in rejection of ESC‐derived tissue. This same treatment exposes activation of macrophages and effector CD8+ T cells, suggesting that these cells are subject to regulatory T cell control. Thus, spontaneous acceptance of ESC‐derived tissues mimics the acquired immune privilege induced by coreceptor blockade and is determined by Treg‐mediated suppression. STEM CELLS 2010;28:1905–1914
Bibliography:Author contributions: K.O.L.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; A.S.B.: data interpretation, manuscript writing, final approval of manuscript; S.P.C.: conception and design; H.W.: conception and design, financial support, administrative support, data analysis and interpretation, manuscript writing, final approval of manuscript; P.J.F.: conception and design, administrative support, data analysis and interpretation, final approval of manuscript. P.J.F. and H.W. contributed equally to this article.
First published online in STEM CELLS
Telephone: 44‐0‐1865‐275‐502; Fax: 44‐0‐1865‐275‐515
Disclosure of potential conflicts of interest is found at the end of this article.
August 24, 2010.
EXPRESS
ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1066-5099
1549-4918
1549-4918
DOI:10.1002/stem.506