Contribution of the PD-1 ligands/PD-1 signaling pathway to dendritic cell-mediated CD4+ T cell activation

✍ Scribed by Harmjan Kuipers; Femke Muskens; Monique Willart; Daniëlle Hijdra; Friso B. J. van Assema; Anthony J. Coyle; Henk C. Hoogsteden; Bart N. Lambrecht

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 318 KB
• Volume: 36
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200635978

✦ Synopsis

Abstract

Dendritic cells (DC) are extremely proficient inducers of naïve CD4^+^ T cell activation due to their high expression level of peptide‐MHC and an array of accessory molecules involved in cell migration, adhesion and co‐signaling, including PD‐1 ligand 1 (PD‐L1) and PD‐1 ligand 2 (PD‐L2). Whether PD‐L1 and PD‐L2 have a stimulatory or inhibitory function is a matter of debate, and could be partially dependent on the model system used. In this study we examined the role of PD‐L1 and PD‐L2 expressed by DC in naïve CD4^+^ T cell activation in a more physiologically relevant model system, using OVA‐specific T cells in combination with various levels of TCR stimulation. Overexpression of PD‐L1 or PD‐L2 by DC did not inhibit T cell proliferation, even when B7–1 and B7–2 mediated costimulation was absent, although IL‐2 production was consistently decreased. Surprisingly, blocking PD‐L1 and PD‐L2 with soluble programmed death‐1 (sPD‐1) also inhibited T cell activation, probably via reverse signaling via PD‐L1 and/or PD‐L2 into DC, leading to reduced DC maturation. This study suggests a relatively minor contribution of PD‐1 ligands in DC‐driven CD4^+^ T cell activation and provides evidence for reverse signaling by PD‐L1 and PD‐L2 into DC, resulting in a suppressive DC phenotype.