J Korean Med Sci.  2013 Dec;28(12):1723-1728. 10.3346/jkms.2013.28.12.1723.

Role of Regulatory T Cells in Transferable Immunological Tolerance to Bone Marrow Donor in Murine Mixed Chimerism Model

Affiliations
  • 1Department of Microbiology and Immunology, Translational Xenotransplantation Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. chgpark@snu.ac.kr

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 gamma-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.

Keyword

Bone Marrow Transplantation; Immune Tolerance; Natural Killer Cells; Regulatory T Cells

MeSH Terms

Animals
Bone Marrow Cells/cytology
*Bone Marrow Transplantation
Cell Proliferation
Chimerism
Cytokines/metabolism
Gamma Rays
Graft Survival
*Immune Tolerance
Killer Cells, Natural/immunology/radiation effects
Leukocytes/immunology/radiation effects
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Models, Animal
Skin Transplantation
T-Lymphocytes, Regulatory/cytology/*immunology/metabolism
Whole-Body Irradiation
Cytokines
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