Abstract
Natural killer (NK) cells play an important role following allogeneic hematopoietic stem cell transplantation (HSCT) exerting graft-versus-leukemia/tumor effect and mediating pathogen-specific immunity. Although NK cells are the first donor-derived lymphocytes reconstituting post-HSCT, their distribution of CD56++CD16− (CD56bright), CD56++CD16+ (CD56intermediate=int), and CD56+CD16++ (CD56dim) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood. The proportion of CD56bright/CD56int/CD56dim changed from 15/8/78% in early childhood to 6/4/90% in adults, respectively. Within this study, we first compared the NK cell reconstitution post-HSCT to reference values of NK cell subpopulations of healthy children. Afterward, we investigated the reconstitution of NK cell subpopulations post-HSCT in correlation to acute graft versus host disease (aGvHD) and chronic graft versus host disease (cGvHD) as well as to viral infections. Interestingly, after a HSCT follow-up phase of 12 months, the distribution of NK cell subpopulations largely matched the 50th percentile of the reference range for healthy individuals. Patients suffering from aGvHD and cGvHD showed a delayed reconstitution of NK cells. Remarkably, within the first 2 months post-HSCT, patients suffering from aGvHD had significantly lower levels of CD56bright NK cells compared to patients without viral infection or without graft versus host disease (GvHD). Therefore, the amount of CD56bright NK cells might serve as an early prognostic factor for GvHD development. Furthermore, a prolonged and elevated peak in CD56int NK cells seemed to be characteristic for the chronification of GvHD. In context of viral infection, a slightly lower CD56 and CD16 receptor expression followed by a considerable reduction in the absolute CD56dim NK cell numbers combined with reoccurrence of CD56int NK cells was observed. Our results suggest that a precise analysis of the reconstitution of NK cell subpopulations post-HSCT might indicate the occurrence of undesired events post-HSCT such as severe aGvHD.
Highlights
The reconstitution of natural killer (NK) cells following allogeneic hematopoietic stem cell transplantation (HSCT) plays an important role in the response against residual malignant cells and the control of viral infections [1, 2]
We investigated the associations between the reconstitution of the three different NK cell subpopulations in regard to the occurrence of events such as acute graft versus host disease or chronic graft versus host disease and severe viral infections in the first year post-HSCT in contrast to a cohort of patients without severe events assumed as control group
The distribution of NK cell subpopulations post-HSCT is divergent from healthy individuals showing a high proportion of CD56bright cells shifting toward CD56dim NK cells
Summary
The reconstitution of natural killer (NK) cells following allogeneic hematopoietic stem cell transplantation (HSCT) plays an important role in the response against residual malignant cells and the control of viral infections [1, 2]. We established reference values of CD56++CD16− (CD56bright), CD56++CD16+ (CD56int), and CD56+CD16++ (CD56dim) NK cells of healthy children and adolescents (n = 174) These reference values were matched and compared to the NK cell reconstitution of patients, who did not suffer from any viral infection or GvHD and are still alive after allogenic stem cell transplantation. We investigated the associations between the reconstitution of the three different NK cell subpopulations in regard to the occurrence of events such as acute graft versus host disease (aGvHD) or chronic graft versus host disease (cGvHD) and severe viral infections in the first year post-HSCT in contrast to a cohort of patients without severe events assumed as control group
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