Nature Medicine
4, 194 - 200 (1998)
doi:10.1038/nm0298-194
Adenovirus-mediated gene transfer into cold-preserved liver allografts: Survival pattern and unresponsiveness following transduction with CTLA4IgKim M. Olthoff1, 5, Thomas A. Judge2, Andrew E. Gelman1, Xiu Da Shen1, Wayne W. Hancock4, Laurence A. Turka3
& Abraham Shaked1
1Department of Surgery, University of Pennsylvania, 4 Silverstein, 3400 Spruce St. Philadelphia, Pennsylvania 19104, USA
2Department of Medicine, Division of Gastroenterology, University of Pennsylvania, 3 Dulles, 3400 Spruce St. Philadelphia, Pennsylvania 19104, USA
3Department of Pathology, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts, 02115 USA
4Department of Medicine, University of Pennsylvania, 901 BRB-1, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
5e-mail, kolthoff@mail.med.upenn.edu The immune response of liver transplant recipients was modulated via adenovirus-mediated transduction of the cold-preserved liver with sequences encoding CTLA4lg. Transplanted allografts demonstrated rapid transient local expression and recombinant protein production shortly after revascularization, resulting in intact liver function, indefinite survival of the recipient, and the development of donor-specific unresponsiveness. Lymphocytic infiltration of the graft was mainly of the T helper 2 (Th2) subset and was not associated with injury to primary cellular targets of the alloimmune response. These findings demonstrate a successful outcome of a feasible and potentially clinically relevant system of gene delivery of sequences encoding proteins capable of inhibiting the alloimmune response.
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