PURPOSE: The failure of in utero transplantation in immune-competent recipients suggests the existence of a fetal immune barrier. The importance of donor major histocompatibility complex (MHC) class I expression in the induction of prenatal tolerance remains undefined. We hypothesized that donor cell MHC class I expression facilitates engraftment in prenatal allogeneic recipients rather than promoting immune rejection. METHODS: B6.Ly5.2 (class I(+)) or B6.TAP(-/-) (class I(-)) murine fetal liver cells were transplanted into age-matched allogeneic fetal recipients. Survival to weaning and subsequent growth was assessed. Engraftment rates and peripheral blood chimerism levels were measured serially. RESULTS: The presence or absence of class I expression did not affect survival or growth of recipients and no graft-vs-host disease developed. Allogeneic recipients of B6.Ly5.2 cells exhibited significantly higher levels of donor hematopoietic chimerism when compared to recipients of B6.TAP(-/-) cells (27% + 10% vs 11% + 8%; P = .004) that deteriorated further over time. CONCLUSIONS: Donor class I MHC antigen expression is essential for stable long-term engraftment and maintenance of donor-specific tolerance. Further studies are needed to better characterize the role of the fetal innate immune system in prenatal allotransplantation.
PURPOSE: The failure of in utero transplantation in immune-competent recipients suggests the existence of a fetal immune barrier. The importance of donor major histocompatibility complex (MHC) class I expression in the induction of prenatal tolerance remains undefined. We hypothesized that donor cell MHC class I expression facilitates engraftment in prenatal allogeneic recipients rather than promoting immune rejection. METHODS: B6.Ly5.2 (class I(+)) or B6.TAP(-/-) (class I(-)) murine fetal liver cells were transplanted into age-matched allogeneic fetal recipients. Survival to weaning and subsequent growth was assessed. Engraftment rates and peripheral blood chimerism levels were measured serially. RESULTS: The presence or absence of class I expression did not affect survival or growth of recipients and no graft-vs-host disease developed. Allogeneic recipients of B6.Ly5.2 cells exhibited significantly higher levels of donor hematopoietic chimerism when compared to recipients of B6.TAP(-/-) cells (27% + 10% vs 11% + 8%; P = .004) that deteriorated further over time. CONCLUSIONS:Donor class I MHC antigen expression is essential for stable long-term engraftment and maintenance of donor-specific tolerance. Further studies are needed to better characterize the role of the fetal innate immune system in prenatal allotransplantation.
Authors: Rebecca H Lian; Motoi Maeda; Stefan Lohwasser; Marc Delcommenne; Toru Nakano; Russell E Vance; David H Raulet; Fumio Takei Journal: J Immunol Date: 2002-05-15 Impact factor: 5.422
Authors: Marcus O Muench; Eva M Pott Bärtsch; Jeng-Chang Chen; John B Lopoo; Alicia Bárcena Journal: Dev Comp Immunol Date: 2003-12 Impact factor: 3.636
Authors: M Manoussaka; A Georgiou; B Rossiter; S Shrestha; J A Toomey; P V Sivakumar; M Bennett; V Kumar; C G Brooks Journal: J Immunol Date: 1997-01-01 Impact factor: 5.422
Authors: Karen P Fraser; Frances Gays; John H Robinson; Katrien van Beneden; Georges Leclercq; Russell E Vance; David H Raulet; Colin G Brooks Journal: Eur J Immunol Date: 2002-03 Impact factor: 5.532
Authors: A W Flake; M G Roncarolo; J M Puck; G Almeida-Porada; M I Evans; M P Johnson; E M Abella; D D Harrison; E D Zanjani Journal: N Engl J Med Date: 1996-12-12 Impact factor: 91.245
Authors: G S Wengler; A Lanfranchi; T Frusca; R Verardi; A Neva; D Brugnoni; S Giliani; M Fiorini; P Mella; F Guandalini; E Mazzolari; S Pecorelli; L D Notarangelo; F Porta; A G Ugazio Journal: Lancet Date: 1996-11-30 Impact factor: 79.321