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.
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/CD56dimchanged 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 CD56brightNK cells compared to patients without viral infection or without graft versus host disease (GvHD). Therefore, the amount of CD56brightNK cells might serve as an early prognostic factor for GvHD development. Furthermore, a prolonged and elevated peak in CD56intNK 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 CD56dimNK cell numbers combined with reoccurrence of CD56intNK 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.
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Huenecke
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cappel
authors.affiliation: GMP Development Unit, Hannover Medical School, Institute of Cellular Therapeutics , Hannover , Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Esser
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Pfirrmann
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Emilia
authors.initials: E
authors.lastname: Salzmann-Manrique
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Sibille
authors.initials: S
authors.lastname: Betz
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Eileen
authors.initials: E
authors.lastname: Keitl
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Banisharif-Dehkordi
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Bakhtiar
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Königs
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jarisch
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Soerensen
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital, Frankfurt, Germany; LOEWE Center for Cell and Gene Therapy, Goethe University, Frankfurt, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ullrich
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital , Frankfurt , Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bremm
keywords: CD16; CD56; NK cells; allogeneic transplantation; children; immune reconstitution; reference values