title: Role of regulatory T cells in transferable immunological tolerance to bone marrow donor in murine mixed chimerism model.
abstract: Constructing a bone marrow chimera prior to graft transplantation can induce donor-specific immune tolerance. Mixed chimerism containing hematopoietic cells of both recipient- and donor-origin has advantages attributed from low dose of total body irradiation. In this study, we explored the mechanism of mixed chimerism supplemented with depletion of Natural Killer cells. Mixed chimerism with C57BL/6 bone marrow cells was induced in recipient BALB/c mice which were given 450 cGy of γ-ray irradiation (n = 16). As revealed by reduced proliferation and cytokine production in mixed leukocyte reaction and ELISpot assay (24.6 vs 265.5), the allo-immune response to bone marrow donor was reduced. Furthermore, the induction of transferable immunological tolerance was confirmed by adoptive transfer and subsequent acceptance of C57BL/6 skin graft (n = 4). CD4(+)FoxP3(+) regulatory T cells were increased in the recipient compartment of the mixed chimera (19.2% → 33.8%). This suggests that regulatory T cells may be therapeutically used for the induction of graft-specific tolerance by mixed chimerism.
authors: Department of Microbiology and Immunology, Translational Xenotransplantation Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Il-Hee
authors: IH
authors: Yoon
authors: Yong-Hee
authors: YH
authors: Kim
authors: You-sun
authors: YS
authors: Kim
authors: Jun-Seop
authors: JS
authors: Shin
authors: Chung-Gyu
authors: CG
authors: Park
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D046528:Chimerism; D016207:Cytokines / Q000378:metabolism; D005720:Gamma Rays; D006085:Graft Survival; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology / Q000528:radiation effects; D007962:Leukocytes / Q000276:immunology / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014916:Whole-Body Irradiation
chemical_list: D016207:Cytokines
keywords: Bone Marrow Transplantation; Immune Tolerance; Natural Killer Cells; Regulatory T Cells