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

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.