Cornea-derived DC are critical for T cell expansion following HSV-1 corneal infection (105.32)

Abstract

Abstract The cornea possesses a resident population of DCs, but their contribution to T cell expansion in draining lymph nodes (DLN) following corneal infection is unknown. Using CD11c-DTR-EGFP mice we were able to locally deplete cornea-resident DC (in cornea before infection) and cornea-derived DC (coming from the cornea after infection (subconjunctival DT) or systemically deplete both corneal and draining lymph node (DLN) resident DC intraperitoneal DT). Depletion of cornea-resident DC did not affect T cell expansion in the DLN. Local depletion of cornea-derived DC through 3 days post infection (dpi) abrogated early CD8+ T cell expansion at 3 dpi, but only reduced CD4+ T cell expansion by 50%. Systemic depletion through 3 dpi completely abrogated early (3 dpi) expansion of both CD4 and CD8 T cells. Depletion of cornea-derived DC through 7 dpi resulted in complete abrogation of both CD4 and CD8 T cell expansion at 7 dpi. We conclude that CD8+ T cells can only be activated by DC that derive from the cornea. CD4+ T cells can be expanded by both cornea-derived and DLN resident DC up to 3 dpi. Both CD4 and CD8+ T cell expansion is dependent on DC transport of viral proteins from the cornea after 3 dpi when free virus is presumably no longer reaching the DLN. Neither local nor systemic DC depletion beyond 7 dpi influenced the development of CD4+ T cell-mediated inflammation in the cornea, suggesting that DC are dispensable for re-stimulation of CD4+ T cells in the cornea