May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Ocular Infiltrating CD4+ T Cells From Patients With Varicella Zoster Virus (VZV) Uveitis Recognize Latency Associated VZV Proteins
Author Affiliations & Notes
  • G. M. Verjans
    Erasmus Medical Center, Rotterdam, The Netherlands
    Virology,
  • J. C. Milikan
    Erasmus Medical Center, Rotterdam, The Netherlands
    Virology,
    Rotterdam Eye Hospital, Rotterdam, The Netherlands
  • S. G. Baarsma
    Rotterdam Eye Hospital, Rotterdam, The Netherlands
  • R. W. A. M. Kuijpers
    Erasmus Medical Center, Rotterdam, The Netherlands
    Ophthalmology,
  • P. R. Kinchington
    Ophthalmology and Visual Science Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
  • A. D. M. E. Osterhaus
    Erasmus Medical Center, Rotterdam, The Netherlands
    Virology,
  • Footnotes
    Commercial Relationships G.M. Verjans, None; J.C. Milikan, None; S.G. Baarsma, None; R.W.A.M. Kuijpers, None; P.R. Kinchington, None; A.D.M.E. Osterhaus, None.
  • Footnotes
    Support SWOO and Prof. Dr. Henkes Stichting (JCM). Public Health Service Grant EY07397, a Core Grant EY08098 from the National Eye Institute and funds from Research to Prevent Blindness Inc., USA (PRK)
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1501. doi:https://doi.org/
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      G. M. Verjans, J. C. Milikan, S. G. Baarsma, R. W. A. M. Kuijpers, P. R. Kinchington, A. D. M. E. Osterhaus; Ocular Infiltrating CD4+ T Cells From Patients With Varicella Zoster Virus (VZV) Uveitis Recognize Latency Associated VZV Proteins. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1501. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Varicella zoster virus (VZV) is a common cause of infectious uveitis, a sight-threatening ocular inflammatory disease. Virus-specific T cells infiltrating the eye are considered to play a role in its pathology, but the VZV antigens recognized are unknown. We determined the functional characteristics and the VZV proteins recognized by T cells recovered from intra-ocular fluid (IOF) samples of VZV-uveitis patients.

Methods:: T cells were recovered from IOF samples and stimulated aspecifically to generate T cell lines (TCL) and subsequently T cell clones (TCC). A comprehensive panel of recombinant vaccinia viruses expressing 11 individual VZV open reading frames (ORF) or parts of ORF62, were used to determine VZV proteins recognized by IOF-derived TCL and TCC obtained from 4 VZV uveitis patients. T cell reactivity was monitored by determining their ability to secrete IFN gamma and kill viral infected cells. Responses of the IOF-derived TCL were compared to the paired peripheral blood (PB)-derived VZV-enriched TCL.

Results:: Whereas the majority of the VZV proteins analyzed were recognized in all VZV-enriched peripheral blood T cell fractions, the paired ocular-derived T cell lines (TCL) in 3 out of 4 patients showed a more restricted VZV protein reactivity. Reactivity to the latency associated VZV proteins ORF4, 29, 62, 63, and additionally to the glycoproteins B (gB) and gE was detected in the ocular-derived TCL. Two new epitopes in ORF62 and one for gE were defined for CD4+ TCC. Diverse HLA-DR and -DQ alleles restricted this local T cell response. Interestingly, one ORF62 epitope was recognized by two genetically different TCC recovered from the same eye in the context of different HLA-DR alleles. Most TCC secreted gamma interferon, but relatively low levels of interleukin 4 and 5. Some TCC had cytolytic T cell activity.

Conclusions:: The results suggest that latency associated VZV proteins, particularly ORF62, are target antigens for CD4+ T cells involved in the intra-ocular T cell responses of the VZV uveitis patients studied.

Keywords: uveitis-clinical/animal model • varicella zoster virus • inflammation 
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