Establishment of a novel method to induce tolerance in adult mice across fully allogeneic (entire H-2 plus multiminor histocompatibility) antigen barriers, using supralethal irradiation followed by injection of syngeneic bone marrow cells plus (donor X recipient) F1 spleen cells.
A novel method was established which can regularly induce profound tolerance in mice across entire H-2 plus multiminor histocompatibility (H) antigen (fully allogeneic) barriers. When recipient AKR/J Sea (AKR; H-2k) or C3H/He Slc (C3H; H-2k) mice were irradiated with 900 rad followed 1 day later by injection of 1 X 10(7) T cell-depleted syngeneic bone marrow cells plus 5 X 10(7) viable, but not mitomycin C-treated, [C57BL/6 Slc(B6) X AKR (or C3H)] F1 spleen cells via intravenous (i.v.) route, a specific tolerant state was induced against B6 (H-2b) antigens. In the tolerant C3H mice, the EL-4 tumor, which originates from B6, was accepted in a tolerogen-specific manner. Moreover, B6 skin grafts were permanently accepted in most of the tolerized AKR and C3H mice. Immunological parameters, including cytotoxic T lymphocyte (CTL) activity and the mixed lymphocyte reaction (MLR), were almost completely suppressed in the tolerant mice. An assay for chimerism using a direct immunofluorescence method revealed that the tolerant AKR mice were chimeric for the first 5 weeks after tolerance induction but not definitely chimeric thereafter. In the tolerant AKR mice, strong suppressor cells were not detected. This method could be used in order to investigate mechanisms of tolerance to allogeneic antigens in future experiments.
Tomita
Y
Y
Department of Immunology, Medical Institute of Bioregulation, Fukuoka, Japan.
Himeno
K
K
Mayumi
H
H
Tokuda
N
N
Nomoto
K
K
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002469:Cell Separation; D002678:Chimera; D005260:Female; D005434:Flow Cytometry; D006183:H-2 Antigens; D007108:Immune Tolerance / Q000528:radiation effects*; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology*; D008937:Mitomycins / Q000378:metabolism; D012882:Skin Tests; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism; D014185:Transplantation, Isogeneic
D006183:H-2 Antigens; D008937:Mitomycins