Rapid reconstitution of NK1 cells after allogeneic transplantation is associated with a reduced incidence of graft-versus-host disease

Abstract

The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Th1, Th2, Th3 and Tr1 cells. Here, we investigate levels of type 1 (IFN-gamma; NK1), type 2 (IL-13; NK2), type 3 (TGF-beta; NK3) and regulatory (IL-10; NKr) cytokines in peripheral blood to assess the cytokine profiles of natural killer (NK) cells following human allogeneic hematopoietic stem cell transplantation (allo-HSCT). NK2 and NK3 cell expansion was observed after allo-HSCT; levels of NKr cells reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT. Multivariate analysis showed that a higher level of NK1 cells by day 15 was associated with a lower overall risk of acute graft-versus-host disease (GVHD) (HR 0.157, P=0.010) as well as II-IV acute GVHD (HR 0.260, P=0.059). Furthermore, higher levels of NK1 cells by day 15 were correlated with lower rates of cytomegalovirus (CMV) reactivation (HR 0.040, 0.005–0.348, P=0.003). These results indicate that rapid reconstitution of NK cells, especially NK1 cells, can help prevent the development of GVHD as well as CMV reactivation after allogeneic transplantation.