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G.M. Verjans, A.D. Osterhaus; Selective Accumulation of Differentiated HSV Serotype Specific CD8+ T Cells Within Human HSV–1 Latently Infected Trigeminal Ganglia . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3072.
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© ARVO (1962-2015); The Authors (2016-present)
Recurrent ocular HSV–1 infections result from reactivation of latent HSV–1 residing life–long in the trigeminal ganglion (TG). In an experimental HSV–1 mouse model, CD8+ T cells have been shown to play a crucial role in maintaining the virus in a latent state. Here, we characterized the local T cell response in human TG samples.
TGs on both sides and blood was obtained from 12 donors within 6 hrs post–mortem. The HSV serostatus was defined by ELISA. Single TG cell suspensions were analyzed by real–time PCR for HSV–1 DNA and HSV–1 latency associated transcript (LAT), IFN–γ, TNF–α, IL–6, perforin, granzyme A and B transcripts. In parallel, TG infiltrating T cells were phenotyped in detail by flowcytometry or used to generate a T cell line by mitogenic stimulation. Virus–specific T cells within the T cell lines were defined by a flowcytometric intra–cellular IFN–γ assay.
Four out of 12 TG donors were HSV seronegative. Presence of HSV–1 DNA, 5034 ± 796 copies/105 TG cells, corresponded both with the donor serostatus and intra–TG HSV–1 LAT expression. Compared to biopsies of genital herpes patients, the expression of perforin, granzyme A and B was significantly lower in the TGs (p<0.0001). The expression of IL–6, IFN–γ or TNF–α was not significantly different. TGs contained 0.4 ± 0.04% CD45+ cells of which about one third co–expressed CD8. The T cells displayed an activated memory/effector phenotype. The intra–TG HSV–specific T cell reactivity was HSV serotype specific and was limited to CD8+ T cells. HSV–specific T cells were not detected in the HSV–1 DNA negative TG–derived T cell lines.
HSV–1 latency in human TG is accompanied with the selective retention of virus–specific CD8+ T cells which may control viral latency by a non–cytolytic pathway.
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