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Identification of Viral Antigens Recognized by Ocular Infiltrating T Cells from Patients with Varicella Zoster Virus-Induced Uveitis

¹From the Institute of Virology and the ⁴Department of Ophthalmology, Erasmus Medical Center, Rotterdam; the ²Rotterdam Eye Hospital, Rotterdam, Netherlands; and the ³Ophthalmology and Visual Science Research Center, University of Pittsburgh, Pennsylvania.

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)- 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 IFN, 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.

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				J. C. M. Milikan, G. S. Baarsma, R. W. A. M. Kuijpers, A. D. M. E. Osterhaus, and G. M. G. M. Verjans Human Ocular-Derived Virus-Specific CD4+ T Cells Control Varicella Zoster Virus Replication in Human Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 743 - 751. [Abstract] [Full Text] [PDF]