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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.

Original publication

DOI

10.1182/blood-2006-07-034157

Type

Journal article

Journal

Blood

Publication Date

01/05/2007

Volume

109

Pages

4080 - 4088

Keywords

Acute Disease, Animals, Antigen-Presenting Cells, Apoptosis, Bone Marrow Transplantation, Endothelium, Graft vs Host Disease, Interferon-gamma, Lymphocyte Activation, Mice, Mice, Knockout, Recovery of Function, T-Lymphocytes, Thymus Gland, Transplantation Chimera, Transplantation, Homologous