Cutting edge: A monoclonal antibody specific for the programmed death-1 homolog prevents graft-versus-host disease in mouse models

J Immunol. 2011 Aug 15;187(4):1537-41. doi: 10.4049/jimmunol.1100660. Epub 2011 Jul 18.

Abstract

Upon interaction with B7 homolog 1, programmed death-1 (PD-1) transmits a critical coinhibitory signal to T cells to negatively regulate immune responses. By extensively searching the genomic database with the IgV region of PD-1, we identified a homolog and named it PD-1 homolog (PD-1H). PD-1H is broadly expressed on the cell surface of hematopoietic cells and could be further upregulated on CD4(+) and CD8(+) T cells following activation. We have generated an mAb against PD-1H, which strikingly prevents acute graft-versus-host disease in semi- and fully allogeneic murine models, leading to full chimerism following treatment. Graft-versus-host disease remains a primary hindrance to successful allogeneic hematopoietic cell transplantation therapy for the treatment of hematologic malignancy. Therefore, manipulation of PD-1H function may provide a new modality for controlling T cell responses to allogeneic tissues in transplant medicine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Murine-Derived / pharmacology*
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Models, Animal
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Mice
  • Programmed Cell Death 1 Receptor
  • Transplantation, Homologous

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor