Modulation of murine herpes simplex virus type 1 retinitis in the uninoculated eye by CD4+ T lymphocytes.

PURPOSE: To investigate the contribution of CD4+ and CD8+ T lymphocytes to retinitis in the contralateral eye after anterior chamber inoculation of herpes simplex virus type 1 (KOS strain). METHODS: T-cell-depleted BALB/c mice were prepared by adult thymectomy and treatment with anti-L3T4 (anti-CD4) monoclonal antibody and/or anti-Lyt2.2 (anti-CD8) monoclonal antibody. On days 9 and 14 after inoculation of herpes simplex virus type 1 (KOS strain) via the anterior chamber, the titer of virus in the uninoculated eye was determined by plaque assay. The eyes were examined microscopically, and the severity of retinitis was evaluated using a histopathologic scoring system. RESULTS: At day 14 postinoculation, significantly less severe destruction of the parenchyma and less inflammatory cell infiltration were observed in the retina of the uninoculated eye of CD4+ T-cell-depleted mice and of mice depleted of both T-cell subsets. The titer of virus in the uninjected eye of CD4+ T-cell-depleted mice and of mice depleted of both CD4+ and CD8+ T cells was also significantly higher at day 14 postinoculation. CONCLUSIONS: The results of the studies suggest three ways CD4+ T cells might contribute to the pathogenesis of herpes simplex virus type 1 retinitis in the uninoculated contralateral eye: (1) accumulation of massive inflammatory cell infiltrates in the retina, (2) induction of retinal destruction, and (3) clearance of herpes simplex virus type 1 from the contralateral eye. In infection of the contralateral retina of nondepleted mice after uniocular anterior chamber inoculation of KOS, CD4+ T cells are required to induce fulminant retinitis and to mediate clearance of virus from the uninoculated eye by day 14 postinoculation. The exact mechanism by which CD4+ T cells contribute to contralateral retinitis remains to be identified.

Duke Scholars

Author Scott William Cousins Ophthalmology, Vitreoretinal Diseases & Surgery