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Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell–mediated immunity
Dallas B. Flies, … , Jessica Jane Ye, Lieping Chen
Dallas B. Flies, … , Jessica Jane Ye, Lieping Chen
Published April 17, 2014
Citation Information: J Clin Invest. 2014;124(5):1966-1975. https://doi.org/10.1172/JCI74589.
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Research Article

Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell–mediated immunity

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Abstract

T cell activation is regulated by the interactions of surface receptors with stimulatory and inhibitory ligands. Programmed death-1 homolog (PD-1H, also called VISTA) is a member of the CD28 family of proteins and has been shown to act as a coinhibitory ligand on APCs that suppress T cell responses. Here, we determined that PD-1H functions as a coinhibitory receptor for CD4+ T cells. CD4+ T cells in mice lacking PD-1H exhibited a dramatically increased response to antigen stimulation. Furthermore, delivery of a PD-1H–specific agonist mAb directly inhibited CD4+ T cell activation both in vitro and in vivo, validating a coinhibitory function of PD-1H. In a murine model of acute hepatitis, administration of a PD-1H agonist mAb suppressed CD4+ T cell–mediated acute inflammation. PD-1H–deficient animals were highly resistant to tumor induction in a murine brain glioma model, and depletion of CD4+ T cells, but not CD8+ T cells, promoted tumor formation. Together, our findings suggest that PD-1H has potential as a target of immune modulation in the treatment of human inflammation and malignancies.

Authors

Dallas B. Flies, Xue Han, Tomoe Higuchi, Linghua Zheng, Jingwei Sun, Jessica Jane Ye, Lieping Chen

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