title: Prediction of reactivity to noninherited maternal antigen in MHC-mismatched, minor histocompatibility antigen-matched stem cell transplantation in a mouse model.
abstract: The immunologic effects of developmental exposure to noninherited maternal Ags (NIMAs) are quite variable. Both tolerizing influence and inducing alloreaction have been observed on clinical transplantation. The role of minor histocompatibility Ags (MiHAs) in NIMA effects is unknown. MiHA is either matched or mismatched in NIMA-mismatched transplantation because a donor of the transplantation is usually limited to a family member. To exclude the participation of MiHA in a NIMA effect for MHC (H-2) is clinically relevant because mismatched MiHA may induce severe alloreaction. The aim of this study is to understand the mechanism of NIMA effects in MHC-mismatched, MiHA-matched hematopoietic stem cell transplantation. Although all offsprings are exposed to the maternal Ags, the NIMA effect for the H-2 Ag was not evident. However, they exhibit two distinct reactivities, low and high responder, to NIMA in utero and during nursing depending on the degree of maternal microchimerism. Low responders survived longer with less graft-versus-host disease. These reactivities were correlated with Foxp3 expression of peripheral blood CD4(+)CD25(+) cells after graft-versus-host disease induction and the number of IFN-γ-producing cells stimulated with NIMA pretransplantation. These observations are clinically relevant and suggest that it is possible to predict the immunological tolerance to NIMA.
authors.affiliation: Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Araki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirayama
authors.forename: Eiichi
authors.initials: E
authors.lastname: Azuma
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kumamoto
authors.forename: Shotaro
authors.initials: S
authors.lastname: Iwamoto
authors.forename: Hidemi
authors.initials: H
authors.lastname: Toyoda
authors.forename: Mitsue
authors.initials: M
authors.lastname: Ito
authors.forename: Keishiro
authors.initials: K
authors.lastname: Amano
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komada
mesh_terms: D000818:Animals; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006183:H-2 Antigens; D015778:Minor Histocompatibility Antigens; D007371:Interferon-gamma