Milikan Johannes C M, Baarsma G Seerp, Kuijpers Robert W A M, Osterhaus Albert D M E, Verjans Georges M G M
Institute of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
Invest Ophthalmol Vis Sci. 2009 Feb;50(2):743-51. doi: 10.1167/iovs.08-2611. Epub 2008 Oct 20.
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.
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-gamma (IFN-gamma), 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-gamma production and cytotoxicity of the TCCs in response to VZV-infected RPE cells was determined by flow cytometry.
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-gamma 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.
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.
水痘带状疱疹病毒（VZV）引起的视网膜炎的特征是视网膜层中存在病毒感染的细胞以及VZV特异性T细胞的眼部浸润。本文探讨了人视网膜色素上皮（RPE）细胞对VZV感染的易感性以及病毒特异性CD4(+) T细胞在体外控制RPE细胞中VZV感染的能力。
用人原代RPE细胞培养物（n = 2）感染表达绿色荧光蛋白的VZV毒株。通过流式细胞术或RPE单层上的荧光成像仪监测感染的RPE细胞的感染情况和活力。用或不用干扰素-γ（IFN-γ）预处理的RPE细胞感染VZV，随后与识别由不同HLA II类等位基因呈递的不同VZV蛋白的VZV特异性CD4(+) T细胞克隆（TCCs；n = 3）一起培养。通过流式细胞术测定TCCs对VZV感染的RPE细胞的IFN-γ产生和细胞毒性。
人RPE细胞允许VZV进行有效感染。只有当RPE细胞用IFN-γ预处理并表达适当的HLA II类等位基因时，VZV感染的RPE细胞才会将同源抗原呈递给CD4(+) TCCs。VZV特异性TCCs抑制RPE细胞中的有效VZV感染，这部分归因于TCC介导的对VZV感染的RPE细胞的杀伤。
所呈现的结果表明，RPE细胞可能在VZV诱导的葡萄膜炎的眼内、VZV特异性、T细胞介导的炎症反应中作为视网膜驻留抗原呈递细胞发挥作用。
