Canine T cells transduced with a herpes simplex virus thymidine kinase gene: A model to study effects on engraftment and control of graft-versus- host disease

George E. Georges, Rainer Storb, Mark W. Brunvand, Hans Peter Kiem, Peter F Moore, Punam Malik, David Ennist, Richard A. Nash

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background. Alloreactive donor T cells in marrow grafts mediate graft- versus-host disease (GVHD), but T-cell depletion has resulted in increased graft failure. Add-back of gene-modified alloreactive donor T cells could prevent graft rejection. After engraftment, in vivo depletion of those modified T cells with ganciclovir may control GVHD. Methods. Canine recipient-specific donor cytotoxic T lymphocytes (CTL) were retrovirally transduced with the herpes simplex virus thymidine kinase gene. Results. Gibbon ape leukemia virus-pseudotyped vector yielded primary CTL transduction efficiency of 22.9±9.9%. After selection and expansion, 96.7±0.8% of CTL expressed retrovirally transferred genes. Recipient-specific cytotoxic activity was maintained with 84.3% specific lysis. After ganciclovir treatment, herpes simplex virus thymidine kinase-transduced CTL proliferation was reduced 98.7±0.2% compared with controls. Conclusions. We have demonstrated efficient ex vivo transduction, expansion, maintenance of alloreactivity, and ganciclovir-mediated ablation of canine CTL, which will permit in vivo studies in the dog, a well-established model for GVHD and engraftment.

Original languageEnglish (US)
Pages (from-to)540-544
Number of pages5
JournalTransplantation
Volume66
Issue number4
DOIs
StatePublished - Aug 27 1998

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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