Bone marrow graft-versus-host disease: early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation
- 1 July 2010
- journal article
- Published by American Society of Hematology in Blood
- Vol. 115 (26), 5401-5411
- https://doi.org/10.1182/blood-2009-11-253559
Abstract
Disrupted hematopoiesis and delayed immune reconstitution are life-threatening complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although graft-versus-host disease (GVHD) is a major risk factor for the bone marrow (BM) insufficiency, how GVHD impairs BM hematopoiesis has been largely unknown. We hypothesized that BM stromal niche could be a target of GVHD. In major histocompatibility complex (MHC)–mismatched murine models of GVHD, we have demonstrated the early destruction of osteoblasts that especially affected B-cell lineages. The defective B lymphopoiesis was due to the impaired ability of BM stroma and osteoblasts to support the hematopoiesis, as evidenced by the failure of GVHD-affected BM to reconstitute the hematopoietic cells. The administration of anti-CD4 monoclonal antibody (mAb) ameliorated these effects and improved B lymphopoiesis while preserving graft-versus-tumor effects. Genetic ablation of Fas–Fas ligand signaling also partially restored B lymphopoiesis. Our present study provided evidence of BM GVHD, with the identification of osteoblasts as the main target for GVHD in BM. Moreover, our data showed the potential for mAb therapies to enhance immune reconstitution in vivo for patients undergoing allo-HSCT.Keywords
This publication has 56 references indexed in Scilit:
- Role of the Osteoblast Lineage in the Bone Marrow Hematopoietic NichesJournal of Bone and Mineral Research, 2009
- Live-animal tracking of individual haematopoietic stem/progenitor cells in their nicheNature, 2008
- Flk2+ common lymphoid progenitors possess equivalent differentiation potential for the B and T lineagesBlood, 2008
- Intervention of MAdCAM-1 or fractalkine alleviates graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effectsJournal of Leukocyte Biology, 2006
- The Lung as a Target Organ of Graft-Versus-Host DiseaseSeminars in Hematology, 2006
- Hemolytic Uremic Syndrome after Bone Marrow Transplantation: Clinical Characteristics and Outcome in ChildrenTransplantation and Cellular Therapy, 2005
- Identification of the haematopoietic stem cell niche and control of the niche sizeNature, 2003
- Osteoblastic cells regulate the haematopoietic stem cell nicheNature, 2003
- Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1Nature, 1996
- THE EFFECT OF THE GRAFT-VERSUS-HOST REACTION ON B LYMPHOCYTE PRODUCTION IN BONE MARROW OF MICETransplantation, 1991