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 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.
Lui
Kathy O
KO
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, United Kingdom.
Boyd
Ashleigh S
AS
Cobbold
Stephen P
SP
Waldmann
Herman
H
Fairchild
Paul J
PJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D007150:Immunohistochemistry; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology