Donor T-cell alloreactivity against host thymic epithelium limits T-cell development after bone marrow transplantation.
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.
Hauri-Hohl
Mathias M
MM
Department of Clinical-Biological Sciences, Laboratory of Pediatric Immunology, University of Basel Children's Hospital, Mattenstrasse 28, 4058 Basel, Switzerland.
Keller
Marcel P
MP
Gill
Jason
J
Hafen
Katrin
K
Pachlatko
Esther
E
Boulay
Thomas
T
Peter
Annick
A
Holländer
Georg A
GA
Krenger
Werner
W
D000208:Acute Disease; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000473:pathology; D017209:Apoptosis / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004727:Endothelium / Q000276:immunology* / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology*; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020127:Recovery of Function / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology; D018183:Transplantation Chimera / Q000276:immunology; D014184:Transplantation, Homologous
D007371:Interferon-gamma