Vascular endothelial growth factor receptor 2-based DNA immunization delays development of herpetic stromal keratitis by antiangiogenic effects.
Stromal keratitis (SK) is an immunoinflammatory eye lesion caused by HSV-1 infection. One essential step in the pathogenesis is neovascularization of the normally avascular cornea, a process that involves the vascular endothelial growth factor (VEGF) family of proteins. In this report, we targeted the proliferating vascular endothelial cells expressing VEGFR-2 in the SK cornea by immunization with recombinant Salmonella typhimurium containing a plasmid encoding murine VEGFR-2. This form of DNA immunization resulted in diminished angiogenesis and delayed development of SK caused by HSV-1 infection and also reduced angiogenesis resulting from corneal implantation with rVEGF. CTL responses against endothelial cells expressing VEGFR-2 were evident in the VEGFR-2-immunized group and in vivo CD8+ T cell depletion resulted in the marked reduction of the antiangiogenic immune response. These results indicate a role for CD8+ T cells in the antiangiogenic effects. Our results may also imply that the anti-VEGFR-2 vaccination approach might prove useful to control pathological ocular angiogenesis and its consequences.
Kim
Bumseok
B
Department of Microbiology and Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Suvas
Susmit
S
Sarangi
Pranita P
PP
Lee
Sujin
S
Reisfeld
Ralph A
RA
Rouse
Barry T
BT
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D003315:Cornea / Q000098:blood supply* / Q000473:pathology / Q000821:virology; D005260:Female; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000276:immunology; D016849:Keratitis, Herpetic / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*
D020533:Angiogenesis Inhibitors; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D040301:Vascular Endothelial Growth Factor Receptor-2