Control of Immune Response to Allogeneic Embryonic Stem Cells by CD3 Antibody–Mediated Operational Tolerance Induction
Year: 2015
Type: article
Abstract: Implantation of embryonic stem cells (ESCs) and their differentiated derivatives into allogeneic hosts triggers an immune response that represents a hurdle to clinical application. We established in autoimmunity and in transplantation that CD3 antibody therapy induces a state of immune tolerance. Promising results have been obtained with CD3 antibodies in the clinic. In this study, we tested whether this strategy can prolong the survival of undifferentiated ESCs and their differentiated derivatives in histoincompatible hosts. Recipients of either mouse ESC-derived embryoid bodies (EBs) or cardiac progenitors received a single short tolerogenic regimen of CD3 antibody. In immunocompetent mice, allogeneic EBs and cardiac progenitors were rejected within 20-25 days. Recipients treated with CD3 antibody showed long-term survival of implanted cardiac progenitors or EBs. In due course, EBs became teratomas, the growth of which was self-limited. Regulatory CD4(+)FoxP3(+) T cells and signaling through the PD1/PDL1 pathway played key roles in the CD3 antibody therapeutic effect. Gene profiling emphasized the importance of TGF-β and the inhibitory T cell coreceptor Tim3 to the observed effect. These results demonstrate that CD3 antibody administered alone promotes prolonged survival of allogeneic ESC derivatives and thus could prove useful for enhancing cell engraftment in the absence of chronic immunosuppression.
DOI: 10.1111/ajt.13477
Institutions: Hôpital Necker-Enfants Malades, Centre National de la Recherche Scientifique, Inserm, Institut Necker Enfants Malades, Sorbonne Paris Cité, Université Paris Descartes, Hôpital Européen Georges-Pompidou, Paris Cardiovascular Research Center, Assistance Publique – Hôpitaux de Paris, Stanford Cardiovascular Institute, Aix-Marseille Université
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,300
Funders: California Institute of Regenerative Medicine, Fondation Leducq, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut Universitaire de France, Tokyo Medical and Dental University, National Institutes of Health, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W2152395298