Eomes ^hi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation

Abstract

Human liver contains an Eomes ^hi population of NK cells that is not present in the blood. In this study, we show that these cells are characterized by a molecular signature that mediates their retention in the liver. By examining liver transplants where donors and recipients are HLA mismatched, we distinguish between donor liver–derived and recipient-derived leukocytes to show that Eomes ^lo NK cells circulate freely whereas Eomes ^hi NK cells are unable to leave the liver. Furthermore, Eomes ^hi NK cells are retained in the liver for up to 13 y. Therefore, Eomes ^hi NK cells are long-lived liver-resident cells. We go on to show that Eomes ^hi NK cells can be recruited from the circulation during adult life and that circulating Eomes ^lo NK cells are able to upregulate Eomes and molecules mediating liver retention under cytokine conditions similar to those in the liver. This suggests that circulating NK cells are a precursor of their liver-resident counterparts.