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

Yl Tracey Chan, Jianmin Zuo, Charlotte Inman, Wayne Croft, Jusnara Begum, Joanne Croudace, Francesca Kinsella, Luke Maggs, Sandeep Nagra, Jane Nunnick, Ben Abbotts, Charles Craddock, Ram Malladi, Paul Moss

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)316-329
Number of pages14
JournalEuropean Journal of Immunology
Volume48
Issue number2
Early online date25 Sep 2017
DOIs
Publication statusPublished - Feb 2018

Keywords

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

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