[The effect of TNF-related apoptosis-inducing ligand on in vivo graft survival after ex vivo adenovirus-mediated gene transfer to cornea].
OBJECTIVE
To observe the effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the allograft rejection after ex vivo adenovirus-mediated gene transfer to cornea.


METHODS
By co-culture with corneal graft, a replication-deficient adenovirus encoding the mTRAIL gene (Ad-TRAIL) was transduced into graft endothelium of mice. Immunohistochemistry was used to look for the TRAIL protein expression in ex vivo corneal endothelium. The grafts obtained from C57BL/6 mice that carried Ad-TRAIL were transplanted into the eyes of BALB/c mice. The occurrence time, the intensity of immunorejection and the immersion of CD4(+) and CD8(+) T lymphocytes were observed. TUNEL was used to detect the cell's apoptosis in the corneal grafts. We used uninfected group, Ad-green-fluorescent protein (GFP) transduced group and soluble death receptor 5 (sDR5) group as controls.


RESULTS
TRAIL protein expression was seen on more than 50% of endothelium 3 days after Ad-TRAIL transduced into corneal grafts in vitro, with higher expression for 2 weeks, then gradually reduced to negative till 3 weeks. The mean time of allograft rejection was 17.7 days in uninfected group, 22 days in Ad-TRAIL group, 17.4 days in Ad-GFP group and 12.3 days in sDR5 group. The differences among four groups were statistically significant. There were distributions of CD4(+), CD8(+) T lymphocytes and apoptotic cells in all rejected corneal grafts.


CONCLUSIONS
TRAIL protein can inhibit corneal allograft rejection in mice and prolong the survival time of transplanted allografts.
Guo
Ping
P
Shandong Eye Institute & Hospital, Qingdao 266071, China.
Xie
Li-xin
LX
Shi
Wei-yun
WY
Li
Xiao-xin
XX
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D003315:Cornea / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015948:Keratoplasty, Penetrating / Q000379:methods*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection / Q000379:methods; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha