| First Author | Le Moine M | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 8 | Pages | 112876 |
| PubMed ID | 37543948 | Mgi Jnum | J:339332 |
| Mgi Id | MGI:7519962 | Doi | 10.1016/j.celrep.2023.112876 |
| Citation | Le Moine M, et al. (2023) Homeostatic PD-1 signaling restrains EOMES-dependent oligoclonal expansion of liver-resident CD8 T cells. Cell Rep 42(8):112876 |
| abstractText | 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. |
