title: Tolerance induction to human stem cell transplants with extension to their differentiated progeny.
abstract: There is increasing interest in transplantation of human stem cells for therapeutic purposes. It would benefit future application if one could achieve their long-term acceptance and functional differentiation in allogeneic hosts using minimal immunosuppression. Allogeneic stem cell transplants differ from conventional tissue transplants insofar as not all alloantigens are revealed during tolerance induction. This risks that the immune system tolerized to antigens expressed by progenitors may still remain responsive to antigens expressed later during differentiation. Here we show that brief induction with monoclonal antibody-mediated coreceptor and costimulation blockade enables long-term engraftment and tolerance towards murine ESCs, hESCs, human induced pluripotent stem cells (iPSCs) and hESC-derived progenitors in outbred murine recipients. Tolerance induced to PSC-derived progenitors extends to their differentiated progenies, and sometimes even to different tissues derived from the same donor. Global gene expression profiling identifies clear features in T cells from tolerized grafts that are distinct from those involved in rejection.
authors.affiliation: 1] Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [3] Department of Chemical Pathology; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors.forename: Kathy O
authors.initials: KO
authors.lastname: Lui
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Duncan
authors.initials: D
authors.lastname: Howie
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Shu-Wing
authors.initials: SW
authors.lastname: Ng
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Shubai
authors.initials: S
authors.lastname: Liu
authors.affiliation: 1] Department of Chemical Pathology; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China [2] Department of Cell and Molecular Biology and Medicine, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D053595:Embryonic Stem Cells / Q000276:immunology / Q000637:transplantation*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D057026:Induced Pluripotent Stem Cells / Q000276:immunology / Q000637:transplantation*; D051379:Mice; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens