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-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.
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-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.
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.
|Number of pages||9|
|Journal||Investigative ophthalmology & visual science|
|Publication status||Published - Feb 2009|
- Antigen-Presenting Cells/physiology
- Antigens, CD/metabolism
- CD4-Positive T-Lymphocytes/immunology
- Cell Line
- Cytotoxicity, Immunologic
- Flow Cytometry
- Green Fluorescent Proteins/metabolism
- Herpes Zoster Ophthalmicus/immunology
- Herpesvirus 3, Human/physiology
- Histocompatibility Antigens Class II/immunology
- Retinal Pigment Epithelium/drug effects
- Viral Proteins/immunology
- Virus Replication