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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1966-1975
Number of pages10
JournalJournal of Clinical Investigation
Volume124
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

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Cellular Immunity
T-Lymphocytes
Ligands
Inflammation
Neoplasms
T-Cell Antigen Receptor
Glioma
Hepatitis
Antigens
Brain
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Flies, D. B., Han, X., Higuchi, T., Zheng, L., Sun, J., Ye, J. J., & Chen, L. (2014). Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell-mediated immunity. Journal of Clinical Investigation, 124(5), 1966-1975. https://doi.org/10.1172/JCI74589

Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell-mediated immunity. / Flies, Dallas B.; Han, Xue; Higuchi, Tomoe; Zheng, Linghua; Sun, Jingwei; Ye, Jessica Jane; Chen, Lieping.

In: Journal of Clinical Investigation, Vol. 124, No. 5, 2014, p. 1966-1975.

Research output: Contribution to journalArticle

Flies, DB, Han, X, Higuchi, T, Zheng, L, Sun, J, Ye, JJ & Chen, L 2014, 'Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell-mediated immunity', Journal of Clinical Investigation, vol. 124, no. 5, pp. 1966-1975. https://doi.org/10.1172/JCI74589
Flies, Dallas B. ; Han, Xue ; Higuchi, Tomoe ; Zheng, Linghua ; Sun, Jingwei ; Ye, Jessica Jane ; Chen, Lieping. / Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell-mediated immunity. In: Journal of Clinical Investigation. 2014 ; Vol. 124, No. 5. pp. 1966-1975.
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