Remodeling specific immunity by use of MHC tetramers: demonstration in a graft-versus-host disease model
| Autor: | Eric G. Pamer, G. Heller, Javier Pinilla-Ibarz, Jeffrey M. Eng, David A. Scheinberg, Adam A. Kochman, Marcel R.M. van den Brink, Ingrid Leiner, Barry J. Kappel, Vanessa M. Hubbard |
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| Rok vydání: | 2005 |
| Předmět: |
Graft Rejection
Male Immunology Population Graft vs Host Disease Biology CD8-Positive T-Lymphocytes Major histocompatibility complex Lymphocyte Activation Biochemistry Lymphocyte Depletion Flow cytometry Major Histocompatibility Complex Mice Immune system medicine Animals Transplantation Homologous Receptor education Bone Marrow Transplantation Cell Proliferation Immunobiology education.field_of_study medicine.diagnostic_test Cell Biology Hematology medicine.disease Transplantation Graft-versus-host disease biology.protein Peptides CD8 |
| Zdroj: | Blood. 107(5) |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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