Donor T-cell Alloreactivity Against Host Thymic Epithelium Limits T-cell Development After Bone Marrow Transplantation.
From: Department of Clinical-Biological Sciences, Laboratory of Pediatric Immunology, University of Basel Children’s Hospital, Mattenstrasse 28, 4058 Basel, Switzerland.
Blood
- Publish Date: May 2007
- ISSN: 0006-4971
- Volume: 109
- Issue: 9
- Pages: 4080-8
- Medium: Print
- Language: English
- Citation (JAMA): Hauri-Hohl Mathias M, Keller Marcel P, Gill Jason, et al. Donor T-cell Alloreactivity Against Host Thymic Epithelium Limits T-cell Development After Bone Marrow Transplantation.. Blood May 2007;109:4080-8
Abstract
Acute graft-versus-host disease (aGVHD) impairs thymus-dependent T-cell regeneration in recipients of allogeneic bone marrow transplants through yet to be defined mechanisms. Here, we demonstrate in mice that MHC-mismatched donor T cells home into the thymus of unconditioned recipients. There, activated donor T cells secrete IFN-gamma, which in turn stimulates the programmed cell death of thymic epithelial cells (TECs). Because TECs themselves are competent and sufficient to prime naive allospecific T cells and to elicit their effector function, the elimination of host-type professional antigen-presenting cells (APCs) does not prevent donor T-cell activation and TEC apoptosis, thus precluding normal thymopoiesis in transplant recipients. Hence, strategies that protect TECs may be necessary to improve immune reconstitution following allogeneic bone marrow transplantation.
Mesh Headings (Keywords): Acute Disease, Animals, Antigen-Presenting Cells, Apoptosis, Bone Marrow Transplantation, Endothelium, Graft vs Host Disease, Interferon Type II, Lymphocyte Activation, Mice, Mice, Knockout, Recovery of Function, T-Lymphocytes, Thymus Gland, Transplantation Chimera, Transplantation, Homologous
Check for Full Text / PubMed Unique Identifier (PMID): 17213290
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