Human ocular-derived virus-specific CD4+ T cells control varicella zoster virus replication in human retinal pigment epithelial cells

Johannes C M Milikan, G Seerp Baarsma, Robert W A M Kuijpers, Albert D M E Osterhaus, Georges M G M Verjans

Research output: Contribution to journalArticleResearchpeer-review


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.

Original languageEnglish
Pages (from-to)743-51
Number of pages9
JournalInvestigative ophthalmology & visual science
Issue number2
Publication statusPublished - 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
  • Humans
  • Interferon-gamma/pharmacology
  • Retinal Pigment Epithelium/drug effects
  • Retinitis/immunology
  • Viral Proteins/immunology
  • Virus Replication


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