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.
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Emily T
ET
Durkin
Kelly A
KA
Jones
Dina
D
Elnaggar
Aimen F
AF
Shaaban
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