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A. Bergua, N. Kittan, S. Haupt, N. Donhauser, K. Korn, F. E. Kruse, B. Schmidt; FACS Analysis of Vitreous Biopsies From Patients With Acute and Subacute Courses of Herpes Virus-Associated Acute Retinal Necrosis Syndrome (ARN). Invest. Ophthalmol. Vis. Sci. 2008;49(13):5134.
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Pathogenesis of ARN is still unclear and involves cellular mechanisms incompletely understood. The first-line recognition of viruses and virus-infected cells is mediated via the innate immune system. An important component are plasmayctoid dendritic cells (PDC), which have been identified as major producers of type I interferons (IFN). We investigated cellular immunologic responses in the vitreous humor obtained from three patients with ARN.
Vitreous humor extracted by pars plana vitrectomy was stained using fluorochrome-conjugated monoclonal antibodies against CD3, CD4, CD8, CD14, CD19, and CD20. PDC were identified as negative for CD11c and CD14, and positive for CD4 and BDCA4 (=CD304). Fluorescent-aided cell sorting (FACS) was performed using a three-color FACS calibur with CellQuest software.
We observed an influx of CD8+ T lymphocytes into the vitreous body in the two cases of acute VZV-associated ARN. In the patient with subacute HSV-2-associated ARN, the CD8+ cell influx was replaced by an influx of B cells and PDC.
Our data showed a lack of PDC infiltration into the vitreous humor in acute episodes of ARN, which may indicate a defective innate immune response contributing to the severity of ARN. Instead, we found an influx of CD8+ cytotoxic T-cells, which may eliminate virus-infected and uninfected cells and thus contribute to viral clearance and retinal destruction. In advanced stages of ARN, PDC were present in the vitreous humor, which may contribute to the orchestration of local immune responses in this immune-privileged compartment. Altogether, our data suggest a role for different cell populations in the course of ARN.
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