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

Alison J. Johnson, Chin Fun Chu, Gregg Milligan

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)9678-9688
Number of pages11
JournalJournal of Virology
Volume82
Issue number19
DOIs
StatePublished - Oct 2008

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Sensory Ganglia
Human herpesvirus 1
Human Herpesvirus 1
spinal cord
Spinal Cord
T-lymphocytes
T-Lymphocytes
Perforin
herpes simplex
nerve tissue
Simplexvirus
mice
viruses
Viral Load
infection
Infection
Viruses
Herpes Genitalis
Virus Diseases
Cellular Structures

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Effector CD4+ T-cell involvement in clearance of infectious herpes simplex virus type 1 from sensory ganglia and spinal cords. / Johnson, Alison J.; Chu, Chin Fun; Milligan, Gregg.

In: Journal of Virology, Vol. 82, No. 19, 10.2008, p. 9678-9688.

Research output: Contribution to journalArticle

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