XIAP deficiency in hematopoietic recipient cells drives donor T-cell activation and GvHD in mice

Eur J Immunol. 2019 Mar;49(3):504-507. doi: 10.1002/eji.201847818. Epub 2019 Jan 3.

Abstract

Patients with X-linked lymphoproliferative syndrome type 2 (XLP-2) (BIRC4 deficiency) suffer from hyperinflammation often observed during the conditioning regimen prior to allogeneic bone marrow transplant. This article shows that in mice hematopoietic recipient cells contribute to graft-versus-host disease by the secretion of elevated levels of proinflammatory cytokines during engraftment when BIRC4 is absent.

Keywords: Graft-versus-host disease; IL-1β; X-linked lymphoproliferative syndrome; allogeneic HSC transplantation; mixed lymphocytes reaction.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation / methods
  • Cytokines / metabolism
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / metabolism
  • Genetic Diseases, X-Linked / therapy*
  • Graft Survival
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / metabolism*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Inflammation Mediators / metabolism
  • Inhibitor of Apoptosis Proteins / deficiency
  • Inhibitor of Apoptosis Proteins / genetics
  • Lymphocyte Activation
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / metabolism
  • Lymphoproliferative Disorders / therapy*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / metabolism*
  • Tissue Donors*
  • Transplantation, Homologous

Substances

  • Birc4 protein, mouse
  • Cytokines
  • Inflammation Mediators
  • Inhibitor of Apoptosis Proteins

Supplementary concepts

  • Lymphoproliferative Syndrome, X-Linked, 2