Remodeling specific immunity by use of MHC tetramers: Demonstration in a graft-versus-host disease model Journal Article
| Authors: | Kappel, B. J.; Pinilla-Ibarz, J.; Kochman, A. A.; Eng, J. M.; Hubbard, V. M.; Leiner, I.; Pamer, E. G.; Heller, G.; van den Brink, M. R. M.; Scheinberg, D. A. |
| Article Title: | Remodeling specific immunity by use of MHC tetramers: Demonstration in a graft-versus-host disease model |
| 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. © 2006 by The American Society of Hematology. |
| Keywords: | survival; controlled study; transplantation, homologous; mortality; nonhuman; cell proliferation; lymphocyte proliferation; t lymphocyte; cd8-positive t-lymphocytes; mouse; animals; mice; morbidity; animal experiment; animal model; allogenic bone marrow transplantation; antineoplastic activity; molecular cloning; lymphocyte activation; immune response; peptides; graft versus host reaction; immunity; graft rejection; major histocompatibility complex; bone marrow transplantation; graft vs host disease; lymphocyte depletion; spleen cell; lymphocyte subpopulation |
| Journal Title: | Blood |
| Volume: | 107 |
| Issue: | 5 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2006-03-01 |
| Start Page: | 2045 |
| End Page: | 2051 |
| Language: | English |
| DOI: | 10.1182/blood-2005-07-2828 |
| PUBMED: | 16269613 |
| PROVIDER: | scopus |
| PMCID: | PMC1895712 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 4 June 2012" - "CODEN: BLOOA" - "Source: Scopus" |
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MSK Authors
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399Heller -
616Van Den Brink -
283Pamer -
49Leiner -
499Scheinberg -
45Kochman -
42
Hubbard -
36
Eng -
30
Pinilla
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