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Johannes C. M. Milikan, G. Seerp Baarsma, Robert W. A. M. Kuijpers, Albert D. M. E. Osterhaus, Georges M. G. M. Verjans; Human Ocular-Derived Virus-Specific CD4+ T Cells Control Varicella Zoster Virus Replication in Human Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(2):743-751. doi: 10.1167/iovs.08-2611.
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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+ T cells to control VZV infection in RPE cells in vitro is addressed.
methods. Human primary RPE cell cultures (n = 2) were infected with a VZV strain expressing green fluorescent protein. 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-γ (IFN-γ), were infected with VZV and subsequently cultured with VZV-specific CD4+ T-cell clones (TCCs; n = 3) recognizing disparate VZV proteins presented by different HLA class II alleles. IFN-γ 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+ TCCs only if the RPE cells were pretreated with IFN-γ 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.
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