The pathogenesis of ocular disease induced by herpes simplex virus Type 1 is poorly understood, in part because of the inherent difficulty in differentiating between immune- and virus-mediated cytopathic effects occurring at the site of infection. The proposed studies involve continued use of a mouse model of herpetic retinitis induced by unilateral anterior chamber inoculation of HSV-1. Characteristic ocular pathology develops, while virus spread to the opposite eye is associated with contralateral retinal necrosis. Systemic immunity is aberrant because anti-HSV delayed hypersensitivity is actively suppressed while anti-HSV antibody responses are intact. Even so, T cells are absolutely essential for ispilateral retinal preservation. We will attempt to determine (1) how systemic immunity induced by intracameral HSV-1 limits virus spread to protect retinas from disease, (2) how the immune system can be manipulated to prevent the pathogenic sequellae of HSV-1 infection, and (3) the intraocular immune elements which may account for ipsilateral protective events or contralateral exacerbation of retinitis and uveitis. A combination of in vivo and in vitro methods with wildtype KOS strain and drug-induced mutants or recombinant strains will be used to identify retinal protective inducer and/or effector T cell subsets and their mechanisms and site(s) of action which limit virus spread. We will attempt to determine the relationship of these protective subpopulation(s) to systemic suppression of delayed hypersensitivity. Herpetic retinitis caused by a number of herpeviruses can produce clinical problems in immunodeficient or immunologically normal patients. Increased understanding of the role of local and systemic immunity in disease pathogenesis after HSV-1 infection is critical for the development of more effective therapeutic measures in herpetic ocular disease.