PSGL-1 Is an Immune Checkpoint Regulator That Promotes T Cell Exhaustion

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2016 May 19

PMID 27192578

Citations 73

Authors

Roberto Tinoco

Florent Carrette

Monique L Barraza

Dennis C Otero

Jonathan Magana

Marcus W Bosenberg

Susan L Swain

Linda M Bradley

Affiliations

Soon will be listed here.

Abstract

Chronic viruses and cancers thwart immune responses in humans by inducing T cell dysfunction. Using a murine chronic virus that models human infections, we investigated the function of the adhesion molecule, P-selectin glycoprotein ligand-1 (PSGL-1), that is upregulated on responding T cells. PSGL-1-deficient mice cleared the virus due to increased intrinsic survival of multifunctional effector T cells that had downregulated PD-1 as well as other inhibitory receptors. Notably, this response resulted in CD4(+)-T-cell-dependent immunopathology. Mechanistically, PSGL-1 ligation on exhausted CD8(+) T cells inhibited T cell receptor (TCR) and interleukin-2 (IL-2) signaling and upregulated PD-1, leading to diminished survival with TCR stimulation. In models of melanoma cancer in which T cell dysfunction occurs, PSGL-1 deficiency led to PD-1 downregulation, improved T cell responses, and tumor control. Thus, PSGL-1 plays a fundamental role in balancing viral control and immunopathology and also functions to regulate T cell responses in the tumor microenvironment.

Citing Articles

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