Remodeling Specific Immunity by Use of Mhc Tetramers: Demonstration in a Graft-versus-host Disease Model.
From: Department of Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, Howard 719, Mailbox 531, 1275 York Ave, New York, NY 10021, USA.
Blood
- Publish Date: Mar 2006
- ISSN: 0006-4971
- Volume: 107
- Issue: 5
- Pages: 2045-51
- Medium: Print
- Language: English
- Citation (JAMA): Kappel Barry J, Pinilla-Ibarz Javier, Kochman Adam A, et al. Remodeling Specific Immunity by Use of Mhc Tetramers: Demonstration in a Graft-versus-host Disease Model.. Blood Mar 2006;107:2045-51
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.
Mesh Headings (Keywords): Animals, Bone Marrow Transplantation, CD8-Positive T-Lymphocytes, Cell Proliferation, Graft Rejection, Graft vs Host Disease, Lymphocyte Activation, Lymphocyte Depletion, Major Histocompatibility Complex, Male, Mice, Peptides, Transplantation, Homologous
Check for Full Text / PubMed Unique Identifier (PMID): 16269613
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