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Updated: May 1, 2026
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
Coinhibitory receptor PD-1H preferentially suppresses CD4⁺ T cell-mediated immunity
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.
Insights
Programmed death-1 homolog (PD-1H) acts as a coinhibitory receptor, suppressing CD4+ T cell responses. Targeting PD-1H with agonists inhibits T cell activation, offering potential for treating inflammation and cancer.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- T cell activation relies on surface receptor interactions with ligands.
- Programmed death-1 homolog (PD-1H), also known as VISTA, is a CD28 family protein.
- PD-1H has been characterized as a coinhibitory ligand on antigen-presenting cells (APCs).
Purpose of the Study:
- To determine the function of PD-1H as a coinhibitory receptor on CD4+ T cells.
- To investigate the therapeutic potential of targeting PD-1H for immune modulation.
Main Methods:
- Analysis of CD4+ T cell responses in PD-1H-deficient mice.
- In vitro and in vivo experiments using PD-1H-specific agonist monoclonal antibodies (mAbs).
- Evaluation of PD-1H agonist efficacy in murine models of acute hepatitis and brain glioma.
Main Results:
- Mice lacking PD-1H showed significantly enhanced T cell responses to antigen stimulation.
- PD-1H agonist mAbs effectively inhibited CD4+ T cell activation in vitro and in vivo.
- PD-1H agonist treatment suppressed CD4+ T cell-mediated inflammation in acute hepatitis.
- PD-1H-deficient mice exhibited resistance to glioma induction, with CD4+ T cell depletion promoting tumor growth.
Conclusions:
- PD-1H functions as a coinhibitory receptor for CD4+ T cells.
- Targeting PD-1H with agonist antibodies can suppress T cell-mediated inflammation and enhance anti-tumor immunity.
- PD-1H represents a promising target for immune modulation in treating human inflammatory diseases and malignancies.
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