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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)
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.
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.
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.
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.
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