title: Immunogenicity and engraftment of mouse embryonic stem cells in allogeneic recipients.
abstract: Embryonic stem cells (ESCs) are pluripotent and therefore able to differentiate both in vitro and in vivo into specialized tissues under appropriate conditions, a property that could be exploited for cellular therapies. However, the immunological nature of these cells in vivo has not been well understood. In vitro, mouse-derived ESCs fail to stimulate T cells, but they abrogate ongoing alloresponses by a process that requires cell-cell contact. We further show that despite a high expression of the NKG2D ligand retinoic acid early inducible-1 by mouse ESCs, they remain resistant to natural killer cell lysis. In vivo, allogeneic mouse ESCs populate the thymus, spleen, and liver of sublethally irradiated allogeneic host mice, inducing apoptosis to T cells and establishing multilineage mixed chimerism that significantly inhibits alloresponses to donor major histocompatibility complex antigens. Immunohistochemical imaging revealed a significant percentage of ESC-derived cells in the splenic marginal zones, but not in the follicles. Taken together, the data presented here reveal that nondifferentiated mouse embryonic stem cells are non-immunogenic and appear to populate lymphoid tissues in vivo, leading to T-cell deletion by apoptosis.
authors.affiliation: Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bonde
authors.forename: Nicholas
authors.initials: N
authors.lastname: Zavazava
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000276:immunology; D033581:Stem Cell Transplantation / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods*