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.