Role of HLA-G and NCR in protection of umbilical cord blood haematopoietic stem cells from NK cell mediated cytotoxicity

Allogeneic umbilical cord blood haematopoietic stem cells (UCB-HSCs) can be transplanted into a host with the intact innate immunity with limited immuno-reaction, although the mechanisms remain unclear. The present studies aimed at investigating potential mechanisms of allogeneic UCB-HSCs escape from the cytolysis of natural killer (NK) cells. We compared UCB-HSCs ability to protect from NK-mediated cytotoxicity with peripheral blood or bone marrow haematopoietic stem cells (PB-HSCs and BM-HSCs). HSCs expressed lower levels of natural cytotoxicity receptor ligands including NKp30L, NKp44L and NKp46L than monocytes. Blocking these ligands respectively or in combination could increase the resistance of HSCs against NK cell mediated cytotoxicity. High expression of HLA-G was noticed on UCB-HSCs, rather than PB-HSCs or BM-HSCs, whereas blockade of HLA-G significantly elevated NK cell mediated cytolysis to UCB-HSCs. Thus, we conclude that natural cytotoxicity receptors and HLA-G on HSCs may contribute to the escape from NK cells, and activate and inhibitory NK cell receptors and their ligands can be novel therapeutic targets in cell transplantation.