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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2045-2051. Prepublished online as a Blood First Edition Paper on November 3, 2005; DOI 10.1182/blood-2005-07-2828. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2828v1 107/5/2045    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kappel, B. J. Articles by Scheinberg, D. A. Search for Related Content PubMed PubMed Citation Articles by Kappel, B. J. Articles by Scheinberg, D. A. Related Collections Immunobiology Neoplasia Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Remodeling specific immunity by use of MHC tetramers: demonstration in a graft-versus-host disease model 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, and David A. Scheinberg From the Department of Molecular Pharmacology and Chemistry and the Department of Medicine, Memorial Sloan-Kettering Cancer Center, and the Department of Pharmacology, Weill Graduate School of Medical Science of Cornell University, New York, NY. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. A. de Witte, M. Toebes, J.-Y. Song, M. C. Wolkers, and T. N. M. Schumacher Effective graft depletion of MiHAg T-cell specificities and consequences for graft-versus-host disease Blood, May 1, 2007; 109(9): 3830 - 3838. [Abstract] [Full Text] [PDF] M. Al-Awwami, T. Sproule, H. Al-Khabbaz, and D. Roopenian The Superdominant Minor Histocompatibility Antigen (MHAg) H60 Recognized by CD8 T Cells Fails to Elicit Lethal Graft Versus Host Disease (GVHD) Regardless of Its Tissue Expression Pattern J. Immunol., April 1, 2007; 178(MeetingAbstracts): S209 - S209.

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