• Citer

Homeostatic PD-1 signaling restrains EOMES-dependent oligoclonal expansion of liver-resident CD8 T cells.

par Le Moine, Marie ;Azouz, Abdulkader ;Sánchez Sánchez, Guillem ;Dejolier, Solange ;Nguyen, Muriel ;Thomas, Séverine ;Shala, Valdrin ;Dreidi, Hacène ;Denanglaire, Sébastien ;Libert, Frédérick ;Vermijlen, David ;Andris, Fabienne ;Goriely, Stanislas
Référence Cell reports, 42, 8, page (112876)
Publication Publié, 2023-08-01

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

The co-inhibitory programmed death (PD)-1 signaling pathway plays a major role in the context of tumor-specific T cell responses. Conversely, it also contributes to the maintenance of peripheral tolerance, as patients receiving anti-PD-1 treatment are prone to developing immune-related adverse events. Yet, the physiological role of the PD-1/PDL-1 axis in T cell homeostasis is still poorly understood. Herein, we show that under steady-state conditions, the absence of PD-1 signaling led to a preferential expansion of CD8+ T cells in the liver. These cells exhibit an oligoclonal T cell receptor (TCR) repertoire and a terminally differentiated exhaustion profile. The transcription factor EOMES is required for the clonal expansion and acquisition of this differentiation program. Finally, single-cell transcriptomics coupled with TCR repertoire analysis support the notion that these cells arise locally from liver-resident memory CD8+ T cells. Overall, we show a role for PD-1 signaling in liver memory T cell homeostasis.