Donor major histocompatibility complex class I expression determines the outcome of prenatal transplantation.
OBJECTIVE
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.
Durkin
Emily T
ET
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Jones
Kelly A
KA
Elnaggar
Dina
D
Shaaban
Aimen F
AF
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D016332:Fetal Tissue Transplantation / Q000276:immunology*; D006084:Graft Rejection; D006085:Graft Survival; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008099:Liver / Q000196:embryology*; D016031:Liver Transplantation / Q000276:immunology* / Q000379:methods; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D014019:Tissue Donors; D018183:Transplantation Chimera; D014181:Transplantation Immunology / Q000502:physiology*; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I