Regulatory T cells control autoimmunity following syngeneic bone marrow transplantation

Authors

  • Angèle Bénard,

    1. Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel, Basel, Switzerland
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  • Rhodri Ceredig,

    1. INSERM U645/UPRES EA2284, IFR 133 Université de Franche-Comté, Etablissement Français du Sang Bourgogne Franche-Comté, Besançon, France
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  • Antonius G. Rolink

    Corresponding author
    1. Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel, Basel, Switzerland
    • Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland, Fax: +41-61-267-1628
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Abstract

Sublethally irradiated, immunodeficient, C57BL/6 RAG-2 gene-deleted recipient mice reconstituted with T cell-depleted bone marrow (BM) grafts frequently developed diarrhea, lost weight and showed signs of autoimmunity, dying between 4 and 7 weeks after reconstitution. Mice died despite evidence of efficient donor-derived hemato-lymphoid reconstitution, and disease was associated with the presence of IgG anti-nuclear antibodies. Autoimmunity was initiated by T cells, but could be prevented by transfer of naturally arising regulatory T cells. In contrast, lethally irradiated, BM-reconstituted immunocompetent, C57BL/6 mice survived without signs of autoimmunity. Survival of immunocompetent mice was shown to be due to the presence of residual, extra-thymically located, radio-resistant, functional regulatory T cells. The importance of regulatory T cells was further shown by the reduced survival of immunocompetent BM recipients whose CD25+ T cells had been depleted prior to bone marrow transplantation. The implications of these results in the context of syngeneic graft-versus-host disease following BM transplantation are discussed.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200636571

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