Corneal-derived dendritic cells are critical in T cell expansion after HSV-1 ocular infection (P6102)

Abstract

Abstract Corneas possess resident DC (cornea-resident DC), and infiltrating DC migrate to the draining lymph nodes (DLN) following HSV-1 corneal infection (cornea-derived DC). The relative contribution of these two DC populations and DLN-resident DC to CD4+ and CD8+ T cell expansion in DLN following HSV-1 corneal infection is unknown. Local depletion of cornea-resident DC in CD11c-DTR mice did not affect T cell expansion in the DLN. Depletion of cornea-derived DC through 3 days post infection (dpi) abrogated early (3 dpi) CD8 T cell expansion (BrdU incorporation), but only reduced CD4 T cell expansion by 50%. Systemic DC depletion through 3 dpi completely abrogated expansion of both CD4 and CD8 T cells at 3 dpi. Depletion of cornea-derived DC through 7 dpi abrogated expansion of both CD4 and CD8 T cell at 7 dpi. Cornea-derived DC showed greater expression of CD70, CD80, and CD86 relative to DLN-resident DC. Blocking CD70 co-stimulation significantly reduced CD8 T cell survival and numbers, but did not affect their proliferation. We conclude that: (i) DC are required for expansion of both HSV-specific CD4+ and CD8+ T cells; (ii) up to 3 dpi CD8 T cells absolutely require HSV-1 presentation by cornea-derived DC possibly due to their enhanced costimulation, whereas DLN-resident DC can stimulate CD4 T cells (presumably with free virus that reaches the DLN from the cornea); (iii) after 3 dpi expansion of both CD4+ and CD8+ T cells requires transport of viral antigens by cornea-derived DC.