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Blood, 1 May 2007, Vol. 109, No. 9, pp. 4080-4088. Prepublished online as a Blood First Edition Paper on January 9, 2007; DOI 10.1182/blood-2006-07-034157.
TRANSPLANTATION Donor T-cell alloreactivity against host thymic epithelium limits T-cell development after bone marrow transplantation1 Department of Clinical-Biological Sciences, Laboratory of Pediatric Immunology, University of Basel, Basel University Children's Hospital (UKBB), Switzerland
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-
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
, 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. 
