Identification of viral antigens recognized by ocular infiltrating T cells from patients with varicella zoster virus-induced uveitis

Johannes C M Milikan, Paul R Kinchington, 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) is a common cause of infectious uveitis associated with an intraocular inflammatory response involving virus-specific T cells. In the current study, the functional characteristics and the antigen specificity of VZV-reactive T cells recovered from intraocular fluid (IOF) samples of five patients with VZV were determined.

METHODS: B-cell lines were infected with a comprehensive panel of recombinant vaccinia viruses expressing 11 individual VZV open reading frames (ORFs), or alternatively pulsed with the corresponding peptides to generate antigen-presenting cells (APCs). T-cell responsiveness of the IOF-derived VZV-specific T cells toward APCs was monitored by interferon (IFN)-gamma enzyme-linked immunosorbent spot-forming assays on bulk T-cell cultures and subsequently T-cell clones (TCCs). The cytokine-secretion profile and cytotoxicity of the VZV-specific TCCs was determined by ELISA and flow cytometry, respectively.

RESULTS: T-cell reactivity to VZV proteins encoded by ORF4, -10, -14, -18, -29, -31, -61, -62, -63, -67, and -68 was demonstrated, but specificity varied individually. T-cell epitopes on ORF62 and -68 were delineated. The TCCs secreted IFNgamma, but relatively low levels of interleukin-4 and -5, in response to VZV antigen-expressing APCs. The TCCs induced antigen-specific cytotoxic T-cell activity.

CONCLUSIONS: The results suggest that the intraocular VZV-specific T-cell response in the patients with VZV analyzed is directed to a broad spectrum of VZV antigens, including the latency-associated VZV proteins from ORFs 4, 29, 63, and particularly ORF62. This local T-cell response was in part mediated by cytotoxic CD4(+) T cells with a Th1/0-like effector memory phenotype.

Original languageEnglish
Pages (from-to)3689-97
Number of pages9
JournalInvestigative ophthalmology & visual science
Issue number8
Publication statusPublished - Aug 2007


  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Antigens, Viral/genetics
  • Aqueous Humor/cytology
  • B-Lymphocytes/cytology
  • Cell Line, Transformed
  • Cytokines/metabolism
  • Epitopes
  • Epitopes, T-Lymphocyte/immunology
  • Female
  • Herpes Zoster/complications
  • Herpesvirus 3, Human/genetics
  • Histocompatibility Antigens Class II/immunology
  • Humans
  • Immunologic Memory/immunology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Open Reading Frames/genetics
  • T-Lymphocytes, Cytotoxic/immunology
  • Th1 Cells/cytology
  • Uveitis/immunology


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