NK cell maturation to CD56dim subset associated with high levels of NCRs overrides the inhibitory effect of NKG2A and recovers impaired NK cell cytolytic potential after allogeneic hematopoietic stem cell transplantation

Abstract

NK cell cytotoxicity against residual leukemic cells is crucial for immune system reconstitution after hematopoietic stem cell transplantation (HSCT). Since immune recovery after transplant still remains a major concern, we studied the counterbalance of NK cell receptors after HSCT and its importance in NK cell functional recovery. We investigated NK cell reconstitution in 27 acute leukemia patients at different time points following HLA-matched allogeneic HSCT compared to those of donors. NK cells were evaluated for their cytotoxicity in a standard 51Cr-release assay against target cells and also analyzed for their receptors expression using flow cytometry. Early after transplant, we found higher percentage of CD56bright NK cells, increased levels of NKG2A and NCRs as well as decreased levels of KIRs expression on NK cells associated with an impaired cytotoxicity of these cells. All the abnormalities were normalized by one year after HSCT when CD56bright NK cells gradually differentiated into CD56dim subset. Collectively, we confirmed a gradual increase of CD56dim NK cells expressing NCRs with the significant decrease in NKG2A expression on NK cells. This finding was also associated with the recovery of NK cell cytotoxicity that suggests an important role for the kinetics of NK cell receptors during cell maturation in HSCT outcome.