A VISTA on PD-1H
Yang Liu
Yang Liu
Published April 17, 2014
Citation Information: J Clin Invest. 2014;124(5):1891-1893. https://doi.org/10.1172/JCI75798.
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Commentary

A VISTA on PD-1H

Abstract

Three years ago, two research groups independently identified a previously undescribed T cell cosignaling molecule; one referred to it as V-domain Ig suppressor of T cell activation (VISTA), and the other used the term programmed death-1 homolog (PD-1H). Recombinant and ectopically expressed PD-1H functions as a coinhibitory ligand for T cell responses. However, the function of endogenous PD-1H is not clear. In this issue of the JCI, Flies and colleagues demonstrate that endogenous PD-1H on both T cells and APCs serves as a coinhibitory molecule for T cell activation and provide further support for targeting PD-1H as a therapeutic strategy for transplantation and cancers.

Authors

Yang Liu

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Figure 1

Models of T cell/T cell interaction.

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Models of T cell/T cell interaction. (A) A new PD-1H–centric model. PD-1...
(A) A new PD-1H–centric model. PD-1H on the surface of T cells and APCs interacts with an unknown receptor(s) on T cells to directly inactivate T cells and confer immune suppression. (B) Classic models of immune activation and immune suppression through modulation of costimulatory activity of APCs. For immune activation, interaction of CD40L expressed on Th cells with CD40 on APCs induces expression of costimulatory molecules, including CD86 and others. The T cells that recognize the same APCs are activated as they are provided with both signal 1 (S1), the cognate antigens (MHC plus peptide [MHCp]), and signal 2 (S2), the costimulatory signal. During immune suppression, Tregs use CTLA-4 to rip CD28 ligands from the surface of APCs. The T cells that recognize the same APC are suppressed as they are provided with only S1, which inactivates T cells through death and anergy (17, 18).