Development of three different NK cell subpopulations during immune reconstitution after pediatric allogeneic hematopoietic stem cell transplantation: prognostic markers in GvHD and viral infections

  • 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.values

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Author:Sabine HüneckeGND, Claudia Cappel, Ruth Esser, Verena PfirrmannGND, Emilia Salzmann-Manrique, Sibille Betz, Eileen Keitl, Julia Banisharif-Dehkordi, Shahrzad Bakhtiar, Christoph KönigsORCiDGND, Andrea Jarisch, Jan Sörensen, Evelyn UllrichORCiDGND, Thomas KlingebielORCiDGND, Peter BaderORCiDGND, Melanie BremmGND
Pubmed Id:
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Research Foundation
Place of publication:Lausanne
Document Type:Article
Year of Completion:2017
Date of first Publication:2017/02/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/03/01
Tag:CD16; CD56; NK cells; allogeneic transplantation; children; immune reconstitution; reference values
Issue:Article 109
Page Number:10
First Page:1
Last Page:10
Copyright © 2017 Huenecke, Cappel, Esser, Pfirrmann, Salzmann-Manrique, Betz, Keitl, Banisharif-Dehkordi, Bakhtiar, Königs, Jarisch, Soerensen, Ullrich, Klingebiel, Bader and Bremm. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0