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| Article Authors: | Barry J Kappel; Javier Pinilla-Ibarz; Adam A Kochman; Jeffrey M Eng; Vanessa M Hubbard; Ingrid Leiner; Eric G Pamer; Glen Heller; Marcel R M van den Brink; David A Scheinberg |
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| Article Title: | Remodeling specific immunity by use of MHC tetramers: demonstration in a graft-versus-host disease model. |
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| Reference ID: | 1020086 |
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| Abstract: | Major histocompatibility complex (MHC) molecules carrying selected peptides will bind specifically to their cognate T-cell receptor on individual clones of reactive T cells. Fluorescently labeled, tetrameric MHC-peptide complexes have been widely used to detect and quantitate antigen-specific T-cell populations via flow cytometry. We hypothesized that such MHC-peptide tetramers could also be used to selectively deplete unique reactive T-cell populations, while leaving the remaining T-cell repertoire and immune response intact. In this report, we successfully demonstrate that a tetramer-based depletion of T cells can be achieved in a murine model of allogeneic bone marrow transplantation. Depletion of a specific alloreactive population of donor splenocytes (< 0.5% of CD8+ T cells) prior to transplantation significantly decreased morbidity and mortality from graft-versus-host disease. There was no early regrowth of the antigen-specific T cells in the recipient and in vivo T-cell proliferation was greatly reduced as well. Survival was increased more than 3-fold over controls, yet the inherent antitumor activity of the transplant was retained. This method also provides the proof-of-concept for similar strategies to selectively remove other unwanted T-cell clones, which could result in novel therapies for certain autoimmune disorders, T-cell malignancies, and solid organ graft rejection. |
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| Affiliations: | Department of Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, Howard 719, Mailbox 531, 1275 York Ave, New York, NY 10021, USA. |
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| Date: | 2006 |
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| Reference Type: | Literature |
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| PubMed ID: | 16269613 |
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| Journal: | Blood |
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| Journal Volume: | 107 |
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| Article Pages: | 2045-51 |
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| Journal ISSN: | 0006-4971 |
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| Article Chemical List: | Peptides |
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| Article MeSH List: | Animals; Bone Marrow Transplantation; CD8-Positive T-Lymphocytes(immunology); Cell Proliferation; Graft Rejection(drug therapy; immunology); Graft vs Host Disease(drug therapy; immunology); Lymphocyte Activation(drug effects; immunology); Lymphocyte Depletion(methods); Major Histocompatibility Complex(immunology); Male; Mice; Peptides(administration & dosage; immunology); Transplantation, Homologous |
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| Curation Last Updated: | 2011-03-31 20:01:25 |
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