CD56 bright NK cell expansion correlated with EBV reactivation control post allogeneic hematopoietic stem cell transplantation

Abstract Natural killer (NK) cells are equipped with anti-Epstein-Barr virus (EBV) function, however，whether EBV infection will affect NK cells reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To identify the characteristics of NK cells, we prospectively enrolled 22 patients with malignant hematological disease who occurred EBV reactivation or not post allo-HSCT. We found that that EBV infection resulted in the expansion of CD56bright and NKG2A+KIR- NK subsets ,and decreased the cytotoxicity function of NK cells. The percentages of NKG2A+KIR- NK cells were higher in patients who progressed into post-transplant lymphoproliferative disorder (PTLD) than EBV viremia patients, which also correlated with decreased proliferation and cytotoxic function. By screening the activation receptors of NK cells, we found the DNAM1+CD56bright NK cells is significantly increased after EBV stimulation. We found that DNAM1 is essential for EBV induced NK cells activation. After blocking DNAM1 on NK cells, the cytokine release against EBV-transformed lymphoblastoid cell lines(EBV-LCL) of CD56bright NK cells were significantly decreased. Anti-DNAM1 of NK cells diminished the clearance of EBV-LCL cells in EBV-related tumor mice model. A prospective cohort showed that old donor age was an independent risk factor for EBV infection. Rapid CD56bri expansion and high expression of DNAM-1 on CD56bri NK cells in response to EBV reactivation correlated with rapid EBV clearance post allo-HSCT in patients with younger donors. In summary, our data showed that high expression of DNAM-1 receptors on NK cell may participate protective CD56bri NK cells response to EBV infection after allo-HSCT.