PURPOSE. Varicella zoster virus (VZV)-induced retinitis is characterized by the presence of virus-infected cells in the retinal layer and the ocular infiltration of VZV-specific T cells. Herein, the susceptibility of human retinal pigment epithelial (RPE) cells to VZV infection and the ability of virus-specific CD4 ϩ T cells to control VZV infection in RPE cells in vitro is addressed. METHODS. Human primary RPE cell cultures (n ϭ 2) were infected with a VZV strain expressing green fluorescent

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... otein. The infection and viability of infected RPE cells was monitored by flow cytometry or by a fluorescent imager on RPE monolayers. RPE cells, pretreated with or without interferon-␥ (IFN-␥), were infected with VZV and subsequently cultured with VZV-specific CD4 ϩ T-cell clones (TCCs; n ϭ 3) recognizing disparate VZV proteins presented by different HLA class II alleles. IFN-␥ production and cytotoxicity of the TCCs in response to VZV-infected RPE cells was determined by flow cytometry. RESULTS. Human RPE cells are permissive to a productive VZV infection. VZV-infected RPE cells presented the cognate antigen to the CD4 ϩ TCCs only if the RPE cells were pretreated with IFN-␥ and expressed the appropriate HLA class II allele. VZV-specific TCCs inhibited productive VZV infection in RPE cells, which was in part attributed to TCC-mediated killing of the VZV-infected RPE cells. CONCLUSIONS. The results presented suggest that RPE cells may play a role as retina-resident antigen-presenting cells in the intraocular, VZV-specific, T cell-mediated inflammatory response of VZV-induced uveitis. (Invest Ophthalmol Vis Sci.