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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 distrib...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300968/ https://www.ncbi.nlm.nih.gov/pubmed/28239380 http://dx.doi.org/10.3389/fimmu.2017.00109 |
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author | Huenecke, Sabine Cappel, Claudia Esser, Ruth Pfirrmann, Verena Salzmann-Manrique, Emilia Betz, Sibille Keitl, Eileen Banisharif-Dehkordi, Julia Bakhtiar, Shahrzad Königs, Christoph Jarisch, Andrea Soerensen, Jan Ullrich, Evelyn Klingebiel, Thomas Bader, Peter Bremm, Melanie |
author_facet | Huenecke, Sabine Cappel, Claudia Esser, Ruth Pfirrmann, Verena Salzmann-Manrique, Emilia Betz, Sibille Keitl, Eileen Banisharif-Dehkordi, Julia Bakhtiar, Shahrzad Königs, Christoph Jarisch, Andrea Soerensen, Jan Ullrich, Evelyn Klingebiel, Thomas Bader, Peter Bremm, Melanie |
author_sort | Huenecke, Sabine |
collection | PubMed |
description | 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(−) (CD56(bright)), CD56(++)CD16(+) (CD56(intermediate=int)), and CD56(+)CD16(++) (CD56(dim)) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood. The proportion of CD56(bright)/CD56(int)/CD56(dim) 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 CD56(bright) NK cells compared to patients without viral infection or without graft versus host disease (GvHD). Therefore, the amount of CD56(bright) NK cells might serve as an early prognostic factor for GvHD development. Furthermore, a prolonged and elevated peak in CD56(int) 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 CD56(dim) NK cell numbers combined with reoccurrence of CD56(int) 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. |
format | Online Article Text |
id | pubmed-5300968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53009682017-02-24 Development of Three Different NK Cell Subpopulations during Immune Reconstitution after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Markers in GvHD and Viral Infections Huenecke, Sabine Cappel, Claudia Esser, Ruth Pfirrmann, Verena Salzmann-Manrique, Emilia Betz, Sibille Keitl, Eileen Banisharif-Dehkordi, Julia Bakhtiar, Shahrzad Königs, Christoph Jarisch, Andrea Soerensen, Jan Ullrich, Evelyn Klingebiel, Thomas Bader, Peter Bremm, Melanie Front Immunol Immunology 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(−) (CD56(bright)), CD56(++)CD16(+) (CD56(intermediate=int)), and CD56(+)CD16(++) (CD56(dim)) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood. The proportion of CD56(bright)/CD56(int)/CD56(dim) 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 CD56(bright) NK cells compared to patients without viral infection or without graft versus host disease (GvHD). Therefore, the amount of CD56(bright) NK cells might serve as an early prognostic factor for GvHD development. Furthermore, a prolonged and elevated peak in CD56(int) 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 CD56(dim) NK cell numbers combined with reoccurrence of CD56(int) 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. Frontiers Media S.A. 2017-02-10 /pmc/articles/PMC5300968/ /pubmed/28239380 http://dx.doi.org/10.3389/fimmu.2017.00109 Text en Copyright © 2017 Huenecke, Cappel, Esser, Pfirrmann, Salzmann-Manrique, Betz, Keitl, Banisharif-Dehkordi, Bakhtiar, Königs, Jarisch, Soerensen, Ullrich, Klingebiel, Bader and Bremm. http://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Immunology Huenecke, Sabine Cappel, Claudia Esser, Ruth Pfirrmann, Verena Salzmann-Manrique, Emilia Betz, Sibille Keitl, Eileen Banisharif-Dehkordi, Julia Bakhtiar, Shahrzad Königs, Christoph Jarisch, Andrea Soerensen, Jan Ullrich, Evelyn Klingebiel, Thomas Bader, Peter Bremm, Melanie Development of Three Different NK Cell Subpopulations during Immune Reconstitution after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Markers in GvHD and Viral Infections |
title | Development of Three Different NK Cell Subpopulations during Immune Reconstitution after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Markers in GvHD and Viral Infections |
title_full | Development of Three Different NK Cell Subpopulations during Immune Reconstitution after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Markers in GvHD and Viral Infections |
title_fullStr | Development of Three Different NK Cell Subpopulations during Immune Reconstitution after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Markers in GvHD and Viral Infections |
title_full_unstemmed | Development of Three Different NK Cell Subpopulations during Immune Reconstitution after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Markers in GvHD and Viral Infections |
title_short | Development of Three Different NK Cell Subpopulations during Immune Reconstitution after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Markers in GvHD and Viral Infections |
title_sort | development of three different nk cell subpopulations during immune reconstitution after pediatric allogeneic hematopoietic stem cell transplantation: prognostic markers in gvhd and viral infections |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300968/ https://www.ncbi.nlm.nih.gov/pubmed/28239380 http://dx.doi.org/10.3389/fimmu.2017.00109 |
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