Cornea-infiltrating dendritic cells are critical in CD8+ T cell expansion in the draining lymph nodes following ocular herpes simplex virus-1 infection (MUC7P.750)

Abstract

Abstract The cornea is a mucosal surface that has resident dendritic cells (cornea-resident DC) and DC infiltrate the cornea following herpes simplex virus-1 (HSV-1) infection (cornea-infiltrating DC). Both DC populations could theoretically carry viral antigens to the draining lymph nodes (DLN) for direct expansion of HSV-specific CD8+ T cells or for cross presentation by DLN-resident DC. The expanded CD8+ T cells infiltrate the trigeminal ganglion (TG) and prevent HSV-1 transmission to the brain and lethal encephalitis. Local depletion of cornea-resident DC in CD11c-DTR mice did not affect CD8+ T cell expansion (BrdU incorporation) in the DLN. However, continuous depletion of cornea-infiltrating DC abrogated CD8+ T cell expansion at 3 days post infection (dpi) and dramatically reduced their expansion at 7 dpi, leading to reduced numbers in the TG and increased mortality. Cornea-infiltrating DC in DLN showed increased expression of the costimulatory molecules CD70, CD80, and CD86. Blocking CD70 significantly reduced CD8+ T cell numbers in the DLN, by selectively inhibiting proliferation and survival of those reactive to subdominant HSV-1 epitopes, leading to decreased CD8+ T cell numbers in the TG and increased mortality. Our data are consistent with the notion that cornea-infiltrating DCs transport HSV-1 antigens to the DLN for direct presentation to and expansion of HSV-specific CD8+ T cells, and have a critical role in preventing lethal infections.