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)-γ 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 IFNγ, 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. Copyright

doi.org/10.1167/iovs.07-0020, hdl.handle.net/1765/35758
Investigative Ophthalmology & Visual Science
Erasmus MC: University Medical Center Rotterdam

Milikan, J., Kinchington, P., Baarsma, S., Kuijpers, R., Osterhaus, A., & Verjans, G. (2007). Identification of viral antigens recognized by ocular infiltrating T cells from patients with varicella zoster virus-induced uveitis. Investigative Ophthalmology & Visual Science, 48(8), 3689–3697. doi:10.1167/iovs.07-0020