April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
CD4+ T cell Programming of HSV-Specific CD8+ T Cell Memory
Author Affiliations & Notes
  • R. L. Hendricks
    Univ of Pittsburgh Eye & Ear Inst, Pittsburgh, Pennsylvania
  • G. M. Frank
    Ophthalmology, Graduate Program in Immunology,
    Univ of Pittsburgh Eye & Ear Inst, Pittsburgh, Pennsylvania
  • Footnotes
    Commercial Relationships  R.L. Hendricks, None; G.M. Frank, None.
  • Footnotes
    Support  NIH grants: EY09545, and P30EY008098; and by non-restricted grants from Research to Prevent Blindness, New York, NY, and the Eye and Ear Foundation of Pittsburgh.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 1201. doi:
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      R. L. Hendricks, G. M. Frank; CD4+ T cell Programming of HSV-Specific CD8+ T Cell Memory. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1201.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Herpes simplex virus type 1 (HSV-1) latent infection of sensory neurons provides the source of virus for recurrent herpetic eye disease. The generation and maintenance of a HSV-specific memory CD8+ T cell population is critical for immunosurveillance of HSV-1 latently infected neurons in the trigeminal ganglion (TG). Understanding the role of CD4+ T cells in programming or maintaining CD8+ T cell memory will have important implications for vaccine development.

Methods: : C57BL/6 mice were depleted of CD4+ T cells in vivo starting before or 8 days after HSV-1 corneal infection (8 dpi). The size and functionality of the HSV-specific CD8+ T cell effector and memory populations were tested by gB498-505 tetramer staining and intracellular cytokine staining and flow cytometric analysis following in vitro stimulation

Results: : the lack of early (prior to 8 dpi) CD4+ T cell "programming" gave rise to HSV-specific CD8+ T cell effector (8 dpi) and early memory (≤ 34 dpi) populations in TG that were quantitatively normal, but exhibited functional compromise (responded only to a high epitope density despite normal TCR affinity) mediated by PD-1/PD-L1 interaction. The CD8+ T cell functional compromise was transient (recovered by 56 dpi) and associated with failure to maintain viral latency. Late CD4+ T cell depletion (beginning 8 dpi) had no effect on CD8+ T cell memory or viral latency.

Conclusions: : CD4+ T cells are needed for programming, but not for the maintenance of HSV-specific CD8+ T cell memory. PD-1 expression inhibits the capacity of unhelped CD8+ T cells to respond to low epitope densities likely present on latently infected neurons, and compromises their ability to maintain HSV-1 latency.

Keywords: immunomodulation/immunoregulation • herpes simplex virus • microbial pathogenesis: experimental studies 

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