Study on the immunological characteristics of PD-1+ regulatory T cells in human liver

Abstract

Liver is known as an immuno-tolerant organ. Regulatory T (TREG) cells are thought to be involved in this immune tolerance, but few immunologic studies have been conducted in depth. In this study, I obtained liver perfusate from healthy donors during liver transplantation and isolated mononuclear cells. I performed phenotypic and functional immunologic analyses of TREG cells in the liver and found them to be phenotypically more active and functionally more suppressive compared to peripheral blood (PB). And while PD-1 has been well studied in recent years as anti-PD-1 therapies have been actively utilized in cancer treatment, its role in TREG cells is not yet well understood. I characterized TREG cells in the liver based on their expression of PD-1 and performed phenotypic, transcriptomic, and functional analyses of PD-1+ and PD-1- TREG cells and identified unique characteristics of PD-1+ TREG cells in the liver. The results confirmed that PD-1+ TREG cells are phenotypically and transcriptomically more activated and functionally more suppressive than PD-1- Treg cells. I also found that PD-1+ TREG cells in the liver highly express tissue resident markers, unlike PD-1+ TREG cells in the PB, and possess a unique T cell receptor (TCR) repertoire. And when anti-PD-1 treatment was given to TREG cells in the liver, their function was further enhanced. Finally, an increased proportion of PD-1+ cells was observed in TREG cells in the liver in patients with liver cirrhosis. In summary, this study furthered our understanding of TREG cells in the liver and provided a deeper immunologic characterization of PD-1+ TREG cells in particular.