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 Blood, 1 March 2008, Vol. 111, No. 5, pp. 2919-2928.
Prepublished online as a Blood First Edition Paper on November 7, 2007; DOI 10.1182/blood-2007-09-112789.

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TRANSPLANTATION

Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organs

Andreas Beilhack1,2, Stephan Schulz1,3, Jeanette Baker1, Georg F. Beilhack4, Ryosei Nishimura1, Enosh M. Baker1, Gilad Landan1, Edward I. Herman1, Eugene C. Butcher5, Christopher H. Contag6, and Robert S. Negrin1

1 Department of Medicine, Stanford University, Stanford, CA; 2 Department of Medicine II, Würzburg University, Würzburg, Germany; 3 Department of Pathology, Technical University München, München, Germany; 4 Department of Medicine I, Ulm University, Ulm, Germany; and Departments of5 Pathology and 6 Pediatrics, Stanford University, Stanford, CA

In acute graft-versus-host disease (aGVHD), donor T cells attack the recipient's gastrointestinal tract, liver, and skin. We hypothesized that blocking access to distinct lymphoid priming sites may alter the specific organ tropism and prevent aGVHD development. In support of this initial hypothesis, we found that different secondary lymphoid organs (SLOs) imprint distinct homing receptor phenotypes on evolving alloreactive effector T cells in vivo. Yet preventing T-cell entry to specific SLOs through blocking monoclonal antibodies, or SLO ablation, did not alter aGVHD pathophysiology. Moreover, transfer of alloreactive effector T cells into conditioned secondary recipients targeted the intestines and liver, irrespective of their initial priming site. Thus, we demonstrate redundancy of SLOs at different anatomical sites in aGVHD initiation. Only prevention of T-cell entry to all SLOs could completely abrogate the onset of aGVHD.


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