Relation between Acute GVHD and NK Cell Subset Reconstitution Following Allogeneic Stem Cell Transplantation

Evelyn Ullrich; Emilia Salzmann-Manrique; Shahrzad Bakhtiar; Melanie Bremm; Stephanie Gerstner; Eva Herrmann; Peter Bader; Petra Hoffmann; Ernst Holler; Matthias Edinger; Daniel Wolff

doi:10.3389/fimmu.2016.00595

Relation between Acute GVHD and NK Cell Subset Reconstitution Following Allogeneic Stem Cell Transplantation

Front Immunol. 2016 Dec 22:7:595. doi: 10.3389/fimmu.2016.00595. eCollection 2016.

Authors

Affiliations

¹ LOEWE Center for Cell and Gene Therapy, Goethe University, Frankfurt, Germany; Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents Medicine, Hospital of the Goethe University Frankfurt, Frankfurt, Germany.
² Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents Medicine, Hospital of the Goethe University Frankfurt , Frankfurt , Germany.
³ LOEWE Center for Cell and Gene Therapy, Goethe University , Frankfurt , Germany.
⁴ Institute of Biostatistics and Mathematical Modeling, Johann Wolfgang Goethe University , Frankfurt , Germany.
⁵ Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany; Regensburg Center for Interventional Immunology (RCI), University of Regensburg, Regensburg, Germany.

Abstract

One of the major challenges of allogeneic stem cell transplantation (allo-SCT) is to reduce the risk of graft-versus-host disease (GVHD) while boosting the graft-versus-leukemia (GVL) effect. The reconstitution of natural killer (NK) cells following allo-SCT is of notable interest due to their known capability to induce GVL without GVHD. Here, in this study, we investigate the association between the incidence and severity of acute graft-versus-host disease (aGVHD) and the early reconstitution of NK cell subsets following allo-SCT. We analyzed 342 samples from 107 patients using flow cytometry, with a focus on immature CD56^high and mature cytotoxic CD56^dim NK cells. Longitudinal analysis of immune reconstitution after allo-SCT showed that the incidence of aGVHD was associated with a delayed expansion of the entire NK cell population, in particular the CD56^high subset. Notably, the disturbed reconstitution of the CD56^high NK cells also correlated with the severity of aGVHD.

Keywords: GVHD; NK cell; NK cell subset; SCT; immune reconstitution.