CD8+ T cells suppress viral replication in the cornea but contribute to VEGF-C-induced lymphatic vessel genesis.
HSV-1 is the leading cause of infectious corneal blindness in the industrialized world. CD4(+) T cells are thought to be the major leukocyte population mediating immunity to HSV-1 in the cornea as well as the likely source of immunopathology that reduces visual acuity. However, the role of CD8(+) T cells in immune surveillance of the cornea is unclear. Thus, we sought to evaluate the role of CD8(+) T cells in ocular immunity using transgenic mice in which >98% of CD8(+) T cells are specific for the immunodominant HSV-1 epitope (gBT-I.1). We found a significant reduction in virus, elevation in HSV-specific CD8(+) T cell influx, and more CD8(+) T cells expressing CXCR3 in the cornea of transgenic mice compared with those in the cornea of wild-type controls yet similar acute corneal pathology. However, by day 30 postinfection, wild-type mice had drastically more blood and lymphatic vessel projections into the cornea compared with gBT-I.1 mice, in which only lymphatic vessel growth in response to VEGF-C could be appreciated. Taken together, these results show that CD8(+) T cells are required to eliminate virus more efficiently from the cornea but play a minimal role in immunopathology as a source of VEGF-C.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Christopher D
CD
Conrady
Min
M
Zheng
Donald U
DU
Stone
Daniel J J
DJ
Carr
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002522:Chlorocebus aethiops; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D016849:Keratitis, Herpetic / Q000473:pathology* / Q000517:prevention & control* / Q000821:virology; D008198:Lymph Nodes / Q000254:growth & development / Q000276:immunology / Q000473:pathology; D042583:Lymphangiogenesis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D042582:Vascular Endothelial Growth Factor C / Q000502:physiology*; D014779:Virus Replication / Q000276:immunology*
D042582:Vascular Endothelial Growth Factor C; C467483:vascular endothelial growth factor C, mouse