Remodeling specific immunity by use of MHC tetramers: Demonstration in a graft-versus-host disease model Academic Article uri icon

Overview

MeSH Major

  • Bone Marrow Transplantation
  • CD8-Positive T-Lymphocytes
  • Graft vs Host Disease
  • Lymphocyte Activation
  • Major Histocompatibility Complex
  • Peptides

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.

publication date

  • March 2006

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1895712

Digital Object Identifier (DOI)

  • 10.1182/blood-2005-07-2828

PubMed ID

  • 16269613

Additional Document Info

start page

  • 2045

end page

  • 51

volume

  • 107

number

  • 5