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

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...

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Autores principales: Yoon, Il-Hee, Kim, Yong-Hee, Kim, You-sun, Shin, Jun-Seop, Park, Chung-Gyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Academy of Medical Sciences 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857366/
https://www.ncbi.nlm.nih.gov/pubmed/24339700
http://dx.doi.org/10.3346/jkms.2013.28.12.1723
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author Yoon, Il-Hee
Kim, Yong-Hee
Kim, You-sun
Shin, Jun-Seop
Park, Chung-Gyu
author_facet Yoon, Il-Hee
Kim, Yong-Hee
Kim, You-sun
Shin, Jun-Seop
Park, Chung-Gyu
author_sort Yoon, Il-Hee
collection PubMed
description 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.
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spelling pubmed-38573662013-12-11 Role of Regulatory T Cells in Transferable Immunological Tolerance to Bone Marrow Donor in Murine Mixed Chimerism Model Yoon, Il-Hee Kim, Yong-Hee Kim, You-sun Shin, Jun-Seop Park, Chung-Gyu J Korean Med Sci Original Article 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. The Korean Academy of Medical Sciences 2013-12 2013-11-26 /pmc/articles/PMC3857366/ /pubmed/24339700 http://dx.doi.org/10.3346/jkms.2013.28.12.1723 Text en © 2013 The Korean Academy of Medical Sciences. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Yoon, Il-Hee
Kim, Yong-Hee
Kim, You-sun
Shin, Jun-Seop
Park, Chung-Gyu
Role of Regulatory T Cells in Transferable Immunological Tolerance to Bone Marrow Donor in Murine Mixed Chimerism Model
title Role of Regulatory T Cells in Transferable Immunological Tolerance to Bone Marrow Donor in Murine Mixed Chimerism Model
title_full Role of Regulatory T Cells in Transferable Immunological Tolerance to Bone Marrow Donor in Murine Mixed Chimerism Model
title_fullStr Role of Regulatory T Cells in Transferable Immunological Tolerance to Bone Marrow Donor in Murine Mixed Chimerism Model
title_full_unstemmed Role of Regulatory T Cells in Transferable Immunological Tolerance to Bone Marrow Donor in Murine Mixed Chimerism Model
title_short Role of Regulatory T Cells in Transferable Immunological Tolerance to Bone Marrow Donor in Murine Mixed Chimerism Model
title_sort role of regulatory t cells in transferable immunological tolerance to bone marrow donor in murine mixed chimerism model
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857366/
https://www.ncbi.nlm.nih.gov/pubmed/24339700
http://dx.doi.org/10.3346/jkms.2013.28.12.1723
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