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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.

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Submitted July 7, 2006
Accepted December 22, 2006

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

Mathias M. Hauri-Hohl, Marcel P. Keller, Jason Gill, Katrin Hafen, Esther Pachlatko, Thomas Boulay, Annick Peter, Georg A. Hollander, and Werner Krenger*

Department of Clinical-Biological Sciences, Laboratory of Pediatric Immunology, University of Basel and Basel University Children's Hospital, Basel, Switzerland

* Corresponding author; email: werner.krenger{at}unibas.ch.

Acute graft-vs.-host disease (aGVHD) impairs thymus-dependent T-cell regeneration in recipients of allogeneic bone marrow transplantation (BMT) 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 (TEC). As TECs themselves are competent and sufficient to prime naive allospecific T-cells and to elicit their effector function, the elimination of host-type professional APC 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 BMT.


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