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Effector CD4+ T-cell involvement in clearance of infectious herpes simplex virus type 1 from sensory ganglia and spinal cords.

TitleEffector CD4+ T-cell involvement in clearance of infectious herpes simplex virus type 1 from sensory ganglia and spinal cords.
Publication TypeJournal Article
Year of Publication2008
AuthorsJohnson AJ, Chu C-F, Milligan GN
JournalJ Virol
Volume82
Issue19
Pagination9678-88
Date Published2008 Oct
ISSN1098-5514
KeywordsAnimals, Antigens, CD95, Brain, CD4-Positive T-Lymphocytes, Fas Ligand Protein, Ganglia, Sensory, Granzymes, Herpesviridae Infections, Herpesvirus 1, Human, Mice, Mice, Inbred C57BL, Models, Biological, Perforin, Spinal Cord
Abstract

<p>In primary infection, CD8(+) T cells are important for clearance of infectious herpes simplex virus (HSV) from sensory ganglia. In this study, evidence of CD4(+) T-cell-mediated clearance of infectious HSV type 1 (HSV-1) from neural tissues was also detected. In immunocompetent mice, HSV-specific CD4(+) T cells were present in sensory ganglia and spinal cords coincident with HSV-1 clearance from these sites and remained detectable at least 8 months postinfection. Neural CD4(+) T cells isolated at the peak of neural infection secreted gamma interferon, tumor necrosis factor alpha, interleukin-2 (IL-2), or IL-4 after stimulation with HSV antigen. HSV-1 titers in neural tissues were greatly reduced over time in CD8(+) T-cell-deficient and CD8(+) T-cell-depleted mice, suggesting that CD4(+) T cells could mediate clearance of HSV-1 from neural tissue. To examine possible mechanisms by which CD4(+) T cells resolved neural infection, CD8(+) T cells were depleted from perforin-deficient or FasL-defective mice. Clearance of infectious virus from neural tissues was not significantly different in perforin-deficient or FasL-defective mice compared to wild-type mice. Further, in spinal cords and brains after vaginal HSV-1 challenge of chimeric mice expressing both perforin and Fas or neither perforin nor Fas, virus titers were significantly lower than in control mice. Thus, perforin and Fas were not required for clearance of infectious virus from neural tissues. These results suggest that HSV-specific CD4(+) T cells are one component of a long-term immune cell presence in neural tissues following genital HSV-1 infection and play a role in clearance of infectious HSV-1 at neural sites, possibly via a nonlytic mechanism.</p>

DOI10.1128/JVI.01159-08
Alternate JournalJ. Virol.
Citation KeyCK104
PubMed ID18667492
PubMed Central IDPMC2546982
Grant ListR01 AI042815 / AI / NIAID NIH HHS / United States
R01 AI054444 / AI / NIAID NIH HHS / United States
AI054444 / AI / NIAID NIH HHS / United States
AI42815 / AI / NIAID NIH HHS / United States