title: The effect of cellular immune tolerance to HSV-1 antigens on the immunopathology of HSV-1 keratitis.
abstract: Previous studies have revealed that herpes simplex virus type 1 (HSV-1) corneal stromal lesions do not develop in the absence of a cell-mediated immune (CMI) response to HSV-1 antigens. HSV-1 glycoprotein C (gC) has been shown to play an important role in the induction of the cytotoxic T lymphocyte (CTL) response to HSV-1 infections at anatomical sites other than the eye. Here we report that a deletion mutant lacking gC (gC-39) when used to infect the corneas of A/J mice was a poor inducer of both CTL and delayed type hypersensitivity (DTH) responses. We have also followed histologically and immunohistochemically the course of HSV-1 stromal disease in A/J mice following topical corneal (TC) infection with wild type (WT) HSV-1, TC infection with gC-39 HSV-1, and simultaneous TC and anterior chamber (TC + AC) infection with WT HSV-1. The latter type of infection has been shown to induce a profound state of DTH and CTL tolerance of HSV-1 antigens. Following TC infection with WT HSV-1, stromal disease progressed to severe ulcerative keratitis with neovascularization by day 21. Histologic and immunohistochemical analysis revealed a predominantly mononuclear infiltrate consisting of numerous plasma cells as well as L3T4+ (T helper/inducer) and Lyt-2+ (T suppressor/cytotoxic) T lymphocytes. Following TC infection with gC-39, or simultaneous TC + AC infection with WT HSV-1, the severity of stromal disease did not progress beyond day 7. On day 21, there was at most a mild stromal cellular infiltrate consisting predominantly of polymorphonuclear neutrophils. These findings indicate that early stromal disease consists of a nonspecific inflammatory response, but severe stromal disease involves a CMI response to HSV-1. AC injection of HSV-1 inhibits the CMI response, thereby halting the progression of stromal disease. Similarly, gC-39, a poor inducer of CMI responses, is also a poor inducer of stromal disease.
authors.affiliation: Department of Ophthalmology, Lions of Illinois Eye Research Institute, University of Illinois College of Medicine, Chicago 60612.
authors.forename: R L
authors.initials: RL
authors.lastname: Hendricks
authors.forename: R J
authors.initials: RJ
authors.lastname: Epstein
authors.forename: T
authors.initials: T
authors.lastname: Tumpey
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D002872:Chromosome Deletion; D003315:Cornea / Q000473:pathology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D007635:Keratitis, Dendritic / Q000150:complications / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D000956:Antigens, Viral; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1