Rapid reconstitution of NK1 cells after allogeneic transplantation is associated with a reduced incidence of graft-versus-host disease
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.
KeywordsNK1 NK2 NK3 NKr GVHD CMV
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The authors thank the members of the core facilities at the Peking University Institute of Hematology for sample collection. This work was supported by the National Natural Science Foundation of China (81270644, 81670166, 81230013, 81530046), the Beijing Talents fund (2015000021223ZK26), the Major State Basic Research Development Program of China (2013CB733700) and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001). The study was also partially supported by the Collaborative Innovation Center of Hematology, China.
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