title: Trogocytosis as a mechanistic link between chimerism and prenatal tolerance.
abstract: In utero hematopoietic cellular transplantation (IUHCT) holds great promise for the treatment of congenital diseases of cellular dysfunction such as sickle cell disease, immunodeficiency disorders and inherited metabolic disorders. However, repeated failures in clinical cases of IUHCT that do not involve an immunodeficiency disease force a closer examination of the fetal immune system. While the mechanisms regulating T cell tolerance have been previously studied, the educational mechanisms leading to NK cell tolerance in prenatal chimeras remain unknown. As a low level of donor cells (1.8%) is required to induce and maintain this tolerance, it is likely that these mechanisms employ indirect host-donor interaction. This report examines donor-to-host MHC transfer (trogocytosis) as an intrinsic mechanism regulating the development and maintenance of NK cell tolerance in prenatal chimeras. The findings demonstrate that phenotypically tolerant host NK cells express low levels of transferred donor MHC antigens during development and later as mature cytotoxic lymphocytes. Further study is needed to understand how the cis-recognition of transferred donor MHC ligand influences the selection and maintenance of tolerant NK cells in prenatal chimeras.
authors.affiliation: Department of Surgery; University of Iowa Carver College of Medicine; Iowa City, IA USA.
authors.forename: Amir M
authors.initials: AM
authors.lastname: Alhajjat
authors.affiliation: Department of Surgery; Cincinnati Children's Hospital Medical Center; Cincinnati, OH USA.
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Strong
authors.affiliation: Department of Surgery; Boston Children's Hospital; Boston, MA USA.
authors.forename: Emily T
authors.initials: ET
authors.lastname: Durkin
authors.affiliation: Department of Surgery; Cincinnati Children's Hospital Medical Center; Cincinnati, OH USA.
authors.forename: Lucas E
authors.initials: LE
authors.lastname: Turner
authors.affiliation: Department of Surgery; Cincinnati Children's Hospital Medical Center; Cincinnati, OH USA.
authors.forename: Ram K
authors.initials: RK
authors.lastname: Wadhwani
authors.affiliation: Department of Surgery; Cincinnati Children's Hospital Medical Center; Cincinnati, OH USA.
authors.forename: Emily F
authors.initials: EF
authors.lastname: Midura
authors.affiliation: Department of Surgery; Cincinnati Children's Hospital Medical Center; Cincinnati, OH USA.
authors.forename: Sundeep G
authors.initials: SG
authors.lastname: Keswani
authors.affiliation: Department of Surgery; Cincinnati Children's Hospital Medical Center; Cincinnati, OH USA.
authors.forename: Aimen F
authors.initials: AF
authors.lastname: Shaaban
mesh_terms: D000818:Animals; D046528:Chimerism / Q000196:embryology*; D004622:Embryo, Mammalian / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000276:immunology; D006087:Graft vs Host Reaction / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D018183:Transplantation Chimera / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I
keywords: MHC; NK cell; chimerism; in utero transplantation; tolerance; trogocytosis