Adenovirus-mediated gene transfer into cold-preserved liver allografts: Survival pattern and unresponsiveness following transduction with CTLA4Ig

Kim M. Olthoff, Thomas A. Judge, Andrew E. Gelman, Xiu Da Shen, Wayne W. Hancock, Laurence A. Turka, Abraham Shaked

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

The immune response of liver transplant recipients was modulated via adenovirus-mediated transduction of the cold-preserved liver with sequences encoding CTLA4Ig. 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.

Original languageEnglish
Pages (from-to)194-200
Number of pages7
JournalNature medicine
Volume4
Issue number2
DOIs
StatePublished - 1998

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