Inhibition of graft-versus-host disease. Use of a T cell-controlled suicide gene.
Graft-vs-host disease (GVHD) after allogeneic bone marrow transplantation is associated with significant morbidity and mortality. T cell depletion of the marrow graft, which is currently used to prevent GVHD, has been shown to result in increased graft failure and leukemia relapse. To explore the feasibility of controlling GVHD, transgenic mice with the herpes simplex virus thymidine kinase suicide gene linked to the IL-2 promoter were used as a source of T cells to induce GVHD, which would be modulated with ganciclovir. Injection of herpes simplex virus thymidine kinase transgenic B10.A(5R) spleen cells into lethally irradiated DBA/2 mice resulted in severe acute GVHD. Treatment of the recipient mice with ganciclovir significantly inhibited GVHD-mediated weight loss and mortality and reduced the severity of inflammation in the target organs of GVHD.
Helene
M
M
Department of Microbiology and Immunology, Chandler Medical Center, University of Kentucky, Lexington 40536, USA. hlbullo@pop.uky.edu
Lake-Bullock
V
V
Bryson
J S
JS
Jennings
C D
CD
Kaplan
A M
AM
D019264:Adoptive Transfer; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D015774:Ganciclovir / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D005814:Genes, Viral; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D018139:Simplexvirus / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D013937:Thymidine Kinase / Q000235:genetics*
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir