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

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

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  • 1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.

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.

PMID:
21768399
[PubMed - indexed for MEDLINE]
PMCID:
PMC3150865
Free PMC Article

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