Mechanistic assessment of PD-1H coinhibitory receptor-induced T cell tolerance to allogeneic antigens

Dallas B. Flies, Tomoe Higuchi, Lieping Chen

Research output: Contribution to journalArticle

Abstract

PD-1H is a recently identified cell surface coinhibitory molecule of the B7/CD28 immune modulatory gene family. We showed previously that single injection of a PD-1H agonistic mAb protected mice from graft-versus-host disease (GVHD). In this study, we report two distinct mechanisms operate in PD-1H-induced T cell tolerance. First, signaling via PD-1H coinhibitory receptor potently arrests alloreactive donor T cells from activation and expansion in the initiation phase. Second, donor regulatory T cells are subsequently expanded to maintain long-term tolerance and GVHD suppression. Our study reveals the crucial function of PD- 1H as a coinhibitory receptor on alloreactive T cells and its function in the regulation of T cell tolerance. Therefore, PD-1H may be a target for the modulation of alloreactive T cells in GVHD and transplantation.

Original languageEnglish (US)
Pages (from-to)5294-5304
Number of pages11
JournalJournal of Immunology
Volume194
Issue number11
DOIs
Publication statusPublished - Jun 1 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

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