title: Extrinsic allospecific signals of hematopoietic origin dictate iNKT cell lineage-fate decisions during development.
abstract: Invariant NKT (iNKT) cells are critical to the maintenance of tolerance toward alloantigens encountered during postnatal life pointing to the existence of a process for self-education. However, the impact of developmentally encountered alloantigens in shaping the phenotype and function of iNKT cells has not been described. To better understand this process, the current report examined naïve iNKT cells as they matured in an allogeneic environment. Following the prenatal transfer of fetal hematopoietic cells between age-matched allogeneic murine fetuses, cell-extrinsic signals appeared to dictate allospecific patterns of Ly49 receptor expression and lineage diversity in developing iNKT cells. Regulation for this process arose from cells of hematopoietic origin requiring only rare exposure to facilitate broad changes in developing iNKT cells. These findings highlight surprisingly asymmetric allospecific alterations in iNKT cells as they develop and mature in an allogeneic environment and establish a new paradigm for study of the self-education of iNKT cells.
authors.affiliation: Department of Surgery, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
authors.forename: Beverly S I
authors.initials: BSI
authors.lastname: Strong
authors.affiliation: Department of Surgery, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
authors.forename: Tess J
authors.initials: TJ
authors.lastname: Newkold
authors.affiliation: Department of Surgery, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Lee
authors.affiliation: Department of Surgery, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
authors.forename: Lucas E
authors.initials: LE
authors.lastname: Turner
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: Amir M
authors.initials: AM
authors.lastname: Alhajjat
authors.affiliation: Departments of Pathology &Immunology and Genetics, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Heusel
authors.affiliation: Department of Surgery, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.|Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: Aimen F
authors.initials: AF
authors.lastname: Shaaban
mesh_terms: D000818:Animals; D019070:Cell Lineage; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000502:physiology* / Q000637:transplantation; D023001:Transplantation Tolerance
chemical_list: D055650:NK Cell Lectin-Like Receptor Subfamily A