Cell-mediated immune tolerance to HSV-1 antigens associated with reduced susceptibility to HSV-1 corneal lesions.
We have investigated the involvement of cell-mediated immune responses to Herpes simplex virus type 1 (HSV-1) in the pathogenesis of HSV-1 induced corneal stromal lesions in mice. Topical corneal (TC) HSV-1 infection induced a vigorous delayed hypersensitivity response, as well as lymphoproliferative and cytotoxic responses in the regional lymph nodes. The cytotoxic response involved HSV-1 specific and genetically restricted cytotoxic T lymphocytes, and activated natural killer cells. Half of the TC HSV-1 infected mice developed corneal stromal inflammation and scarring, the cause of visual morbidity in human herpetic disease. However, injection of HSV-1 into the ocular anterior chamber (AC) prior to, or simultaneously with, TC HSV-1 infection resulted in a profound state of cell-mediated immune tolerance of HSV-1 antigens. The tolerance was characterized by a substantial reduction in delayed hypersensitivity, lymphoproliferative, and cytotoxic responses to HSV-1 and was associated with virtually complete protection from corneal stromal lesions induced by HSV-1. These findings suggest a pathogenetic role for cell-mediated immunity and indicate the feasibility of preventing stromal disease through proper manipulation of the immune response.
Ksander
B R
BR
Department of Microbiology and Immunology, University of Illinois College of Medicine at Chicago 60612.
Hendricks
R L
RL
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D003316:Corneal Diseases / Q000276:immunology*; D003319:Corneal Stroma / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004198:Disease Susceptibility; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007635:Keratitis, Dendritic / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D018139:Simplexvirus / Q000276:immunology*
D000956:Antigens, Viral