title: Cutting edge: A monoclonal antibody specific for the programmed death-1 homolog prevents graft-versus-host disease in mouse models.
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.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Dallas B
authors.initials: DB
authors.lastname: Flies
authors.forename: Shengdian
authors.initials: S
authors.lastname: Wang
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D051379:Mice; D061026:Programmed Cell Death 1 Receptor; D014184:Transplantation, Homologous
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor