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
Georges, G.E.; Storb, R.; Brunvand, M.W.; Kiem, H.P.; Moore, P.F.; Malik, P.; Ennist, D.; Nash, R.A.
Transplantation 66(4): 540-544
1998
ISSN/ISBN: 0041-1337 PMID: 9734503 Document Number: 488812
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.