Asymptomatic ocular herpes infections precipitate rapid rejection of corneal allografts (TRAN3P.917)

Abstract

Abstract Most herpes simplex virus type 1 (HSV-1) infected individuals are asymptomatic despite harboring latent virus in their trigeminal ganglia (TG). To determine if these ‘quiet’ infections influence corneal transplant survival we infected the corneas of C57Bl/6 mice with an HSV-1 strain that causes a latent TG infection but no overt corneal pathology. Infected mice received a corneal transplant from syngeneic mice that express ovalbumin (OVA) as a surrogate alloantigen. Graft survival was 9% in infected mice as compared to 58% in non-infected mice. Transcripts for chemokines including CXCL10, CXCL9, CCL5, and CCL2 were significantly elevated, and were significantly reduced by CD4 T cell depletion prior to infection. To assess CD4 T cell antigen specificity irradiated wild type C57BL/6 mice were reconstituted with mixed BM from CD4 KO mice and RAG-/- OT-II transgenic mice so all CD4 T cells were OVA-specific. The chimeras were not infected or received a quiet HSV-1 infection with or without transfer of polyclonal CD4 T cells prior to transplantation of OVA expressing grafts. Graft survival in chimeras was: 100% (non-infected), 60% (quiet infection, no T cell transfer), and 20% (quiet infection with CD4 T cell transfer). We conclude that quiet HSV-1 corneal infections can augment CD4 T cell mediated corneal allograft rejection by increasing chemokine expression in the graft bed and possibly recruiting HSV-specific CD4 T cells into the rejection response.