Intrathymic inoculation of donor HLA class I-derived peptide generates donor-specific CD4+CD25+ regulatory T cells.
CD4(+)CD25(+) regulatory T cells are selected in the thymus to control autoreactive thymic escapees preventing autoimmunity that cannot be achieved by negative selection or deletion alone, thus playing an important role in the maintenance of immunological homeostasis. Not only significant in preventing autoimmunity, CD4(+)CD25(+) regulatory T cells have also been shown to be involved in allograft tolerance in organ transplantation. We have formerly introduced two lines of HLA class I transgenic mice to elucidate the role of HLA class I molecules in transplantation biology. Using a heterotopic cardiac transplantation model, we show herein that intrathymic inoculation of donor HLA class I-derived synthetic peptide results in the generation of CD4(+)CD25(+) regulatory T cells, which induce graft specific tolerance without any preconditioning of the recipient or use of immunosuppressive drugs. This study provides evidence of the novel therapeutic potential of CD4(+)CD25(+) regulatory T cells for clinical transplantation.
Tamura
S
S
Department of Surgery and Bioengineering, Advanced Clinical Research Center, Institution of Medical Science, University of Tokyo, Tokyo, Japan. sumitmr-tky@umin.ac.jp
Beck
Y
Y
Ando
Y
Y
Tahara
H
H
D000595:Amino Acid Sequence; D000818:Animals; D006085:Graft Survival / Q000276:immunology; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics*; D016027:Heart Transplantation / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology*
D015235:HLA-B Antigens; D010446:Peptide Fragments