[Experimental study of the inhibiting effect of the lentiviral vector mediated herpes simplex virus-thymidine kinase/ganciclovir on GVHD].
OBJECTIVE
To study the effect of lentiviral vector mediated herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) on graft- versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo- BMT) in mice.


METHODS
Donor splenic lymphocytes from C57BL/6 which were infected by lentiviral vectors carrying HSV-TK were transplanted into 60Co gamma ray irradiated recipient mice with donor bone marrow cells. GCV 25 mg x kg(-1) x d(-1) was administered in 3 groups on day 0, +7, +12 respectively after transplant for 7 days by intraperitoneal injection. Survival time, severity of GVHD, incidence of GVHD, T lymphocytes immune reconstruction and of allogeneic chimerism ratio were detected after allo-BMT.


RESULTS
The average survival times for GCV 0 day, +7 day and +12 day group were (30. 10 +/- 5.21) d, (36.40 +/- 5.28) d and (28.20 +/- 4.82) d respectively, being significantly longer than that in the control group [(15.10 +/- 0.43) d] (P < 0.05). The 50 d-survival rate for TK/GCV + 7 day group was 60%. While for 0 day and +12 day group was 40% and 30% respectively. The incidence of grade III approximately IV GVHD in the control group was 100%, and the dead mice in experimental groups showed pathological changes of II approximately III GVHD. Long-term alive recipient mice only developed grade I approximately II GVHD after allo-BMT. The number of CD4+ lymphocytes in experimental groups was higher than that in control group (P <0.05), but CD8+ lymphocytes was lower on day +5, +10, +15 day (P <0.05). Allogeneic chimerism rate of recipient mice on +30 d was 100%.


CONCLUSIONS
HSV-TK/GCV induced by the lentiviral vectors has a definite effect in prevention of GVHD after allo-BMT. GCV administrated from 7 days post-transplantation showed the best effects.
Xu
Kai-lin
KL
Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Zhu
Feng
F
Du
Bing
B
Gao
Fei
F
Cheng
Hai
H
Pan
Xiu-ying
XY
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D015774:Ganciclovir / Q000494:pharmacology*; D005822:Genetic Vectors; D006086:Graft vs Host Disease / Q000517:prevention & control*; D016086:Lentivirus / Q000235:genetics*; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection; D014184:Transplantation, Homologous
D013937:Thymidine Kinase; D015774:Ganciclovir