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Circulating herpes simplex type 1 (HSV-1)-specific CD8+ T cells do not access HSV-1 latently infected trigeminal ganglia.

TitleCirculating herpes simplex type 1 (HSV-1)-specific CD8+ T cells do not access HSV-1 latently infected trigeminal ganglia.
Publication TypeJournal Article
Year of Publication2011
AuthorsHimmelein S, St Leger AJ, Knickelbein JE, Rowe A, Freeman ML, Hendricks RL
JournalHerpesviridae
Volume2
Issue1
Pagination5
Date Published2011 Mar 15
ISSN2042-4280
Abstract

<p><b>BACKGROUND: </b>Therapeutic vaccines can be designed to enhance existing T cell memory populations for increased protection against re-infection. In the case of herpes simplex virus type 1, recurrent disease results from reactivation of latent virus in sensory ganglia, which is controlled in part by a ganglia-resident HSV-specific memory CD8+ T cell population. Thus, an important goal of a therapeutic HSV-1 vaccine would be to enhance this population.</p><p><b>METHODS: </b>HSV-1-infected mice were treated with TAK-779 to block CCR5- and CXCR3-mediated CD8+ T cell migration during both acute and latent infections. Additionally, HSV-1-specific CD8+ T cells were transferred into HSV-1 latently infected mice to mimic the effect of a therapeutic vaccine, and their migration into trigeminal ganglia (TG) was traced during steady-state latency, or during recovery of the TG-resident memory CD8+ T cell population following stress-, and corticosterone-induced depletion and HSV-1 reactivation from latency. Bromodeoxy uridine (BrdU) incorporation measured cell proliferation in vivo.</p><p><b>RESULTS: </b>TAK-779 treatment during acute HSV-1 infection reduced the number of infiltrating CD8+ T cells but did not alter the number of viral genome copies. TAK-779 treatment during HSV latency did not affect the size of the TG-resident memory CD8+ T cell population. Transferred HSV-specific CD8+ T cells failed to access latently infected TG during steady-state latency, or during recovery of the TG resident HSV-specific CD8+ T cell population following exposure of latently infected mice to stress and corticosterone. Recovery of the HSV-specific CD8+ T cell population after stress and corticosterone treatment occurred with homeostatic levels of cell division and did not require CD4+ T cell help.</p><p><b>CONCLUSIONS: </b>Our findings are consistent with the notion that the CD8+ T cells in latently infected TG are a tissue-resident memory (Trm) population that is maintained without replenishment from the periphery, and that when this population is disrupted, it recovers without proliferation or detectable recruitment of HSV-specific CD8+ T cells from the blood. The compartmentalization of the HSV-specific CD8+ memory T cell population in latently infected TG will complicate the design of therapeutic vaccines.</p>

DOI10.1186/2042-4280-2-5
Alternate JournalHerpesviridae
Citation KeyCK105
PubMed ID21429183
PubMed Central IDPMC3070622