Mixed chimerism established by hematopoietic stem cell transplantation is maintained by host and donor T regulatory cells

Research output: Contribution to journalArticle

Authors

  • Hayden Pearce
  • Luke Maggs
  • Y L Tracey Chan
  • Jane Nunnick
  • Sandeep Nagra
  • Mike Griffiths
  • Charles Craddock
  • Ram Malladi

External organisations

  • Department of Clinical Immunology, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
  • Centre for Clinical Haematology, Queen Elizabeth NHS Foundation Trust and Birmingham Health Partners, Birmingham, United Kingdom; and.
  • West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, United Kingdom.

Abstract

Transplantation is an effective treatment of many clinical disorders, but the mechanisms that regulate immunological tolerance are uncertain and remain central to improving patient outcome. Hemopoietic stem cell transplantation (SCT) often establishes "mixed chimerism" in which immune cells from both the donor and patient coexist in vivo in a setting of immunological tolerance. We studied immune function in 69 patients within 2 months following SCT; 37 were fully donor and 32 displayed mixed chimerism. The proportion of T regulatory (Treg) cells was increased during mixed chimerism and comprised equal numbers of donor and host-derived regulatory cells. This was associated with a tolerogenic PD-L1+ profile on dendritic cells. Importantly, effector T cells from patients with mixed chimerism exhibited reduced cytotoxicity against host target cells in vitro, but this was restored following depletion of CD4+ Treg cells. These data show that Treg cells play a major role in sustaining immunological tolerance during mixed chimerism. These insights should help to guide novel interventions to improve clinical transplantation.

Bibliographic note

© 2019 by The American Society of Hematology.

Details

Original languageEnglish
Pages (from-to)734-743
Number of pages10
JournalBlood Advances
Volume3
Issue number5
Publication statusPublished - 12 Mar 2019