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

Authors


  • 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.

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

  • §

    First published online in STEM CELLS EXPRESS August 24, 2010.

Abstract

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

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