NK cells produce high levels of IL-10 early after allogeneic stem cell transplantation and suppress development of acute GVHD

Research output: Contribution to journalArticle

Authors

External organisations

  • Centre for Liver Research, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.
  • Birmingham Health Partners, Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.

Abstract

Natural killer (NK) cells rapidly reconstitute following allogeneic stem cell transplantation (allo-SCT), at the time when alloreactive T cell immunity is being established. We investigated very early NK cell reconstitution in 82 patients following T cell-depleted allo-SCT. NK cell number rapidly increased, exceeding T cell reconstitution such that the NK:T cell ratio was over 40 by day 14. NK cells at day 14 (NK-14) were donor-derived, intensely proliferating and expressed chemokine receptors targeted to lymphoid and peripheral tissue. Spontaneous production of the immunoregulatory cytokine IL-10 was observed in over 70% of cells and transcription of cytokines and growth factors was augmented. NK-14 cell number was inversely correlated with the incidence of grade II-IV acute graft versus host disease (GVHD). These findings reveal that robust reconstitution of immunoregulatory NK cells by day 14 after allo-SCT is an important determinant of the clinical outcome, suggesting that NK cells may suppress the development of the T cell-mediated alloreactive immune response through production of IL-10. This article is protected by copyright. All rights reserved.

Details

Original languageEnglish
Pages (from-to)316-329
JournalEuropean Journal of Immunology
Volume48
Issue number2
Early online date25 Sep 2017
Publication statusPublished - 22 Feb 2018

Keywords

  • T cells depleted, Allo-SCT, GVHD , NK cells , IL-10