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Abstract
PURPOSE: To investigate T cell infiltration in the posterior segment of the uninjected eye after uniocular anterior chamber inoculation of HSV-1. METHODS: The anterior chamber of one eye of euthymic BALB/c mice was injected with 1 x 10(4) plaque-forming units (PFU) to 2 x 10(4) PFU of herpes simplex virus type 1 (HSV-1; KOS strain). All mice were examined for retinitis on day 8 postinoculation (p.i.). Only mice with retinitis were retained and used in these experiments. Animals were killed on days 9, 11, 14, 21, 35, and 63 p.i. The uninjected eyes were removed. Some of the uninjected eyes were sectioned and stained for CD4+ and CD8+ cells using the avidin-biotinylated enzyme complex method. Infiltrating cells were collected from the remaining uninoculated eyes and stained using rat anti-mouse monoclonal antibodies specific for CD4+ or CD8+ T cells, and the percentage of CD4+ and CD8+ T cells was determined by flow cytometry. RESULTS: At day 9 p.i. (acute retinitis), T cells were observed in the uvea but not in the retina of the contralateral eye. CD4+ and CD8+ cells were observed in the sensory retina coincident with the onset of retinal necrosis (day 11 p.i.), and CD4+ and CD8+ T cells continued to be detected in the remnants of the retina up to and including day 63 p.i. The maximum percentage of both CD4+ and CD8+ T cells was observed at day 21 p.i. CONCLUSIONS: These results demonstrate that T cells enter the retina of the uninoculated eye during HSV-1 infection. The observation that T cells arrive in the sensory retina at the onset of retinal necrosis and not during acute retinitis and the peak of virus replication provides further evidence that T cells play a role in development of retinal necrosis. The result that T cells are observed in the uninjected eye as late as day 63 p.i. suggests that T cells might also have a role in the resolution phase of the disease.