Regulatory T cells control autoimmunity following syngeneic bone marrow transplantation.
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.
Bénard
Angèle
A
Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel, Basel, Switzerland.
Ceredig
Rhodri
R
Rolink
Antonius G
AG
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology*; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D001323:Autoantibodies; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse