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Blood. 2007 May 1;109(9):4080-8. Epub 2007 Jan 9.

Donor T-cell alloreactivity against host thymic epithelium limits T-cell development after bone marrow transplantation.

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Department of Clinical-Biological Sciences, Laboratory of Pediatric Immunology, University of Basel Children's Hospital, Mattenstrasse 28, 4058 Basel, 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-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.

[Indexed for MEDLINE]
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