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.