Abstract
Abstract Herpes simplex virus type 1 (HSV-1) infection of mouse corneas leads to establishment of a latent viral infection in sensory neurons of the trigeminal ganglion (TG). Activated CD8+ T cells enter the TG during acute infection and are retained in close apposition to neurons during latency. Fifty percent of the CD8+ T cells in the infected TG of C57BL/6 mice recognize an immunodominant epitope on HSV-1 glycoprotein B (gB498-505), while the remaining CD8+ T cells target subdominant epitopes on 11 other viral proteins. Although both populations appear to be stimulated throughout latency, gB498-505-CD8s show increasing functionality (lytic granule release and IFN-γ and TNF-α production) during latency and appear to have a primary role in blocking HSV-1 reactivation from latency. In contrast, TG CD8+ T cells reactive to subdominant epitopes lose functionality during latency. Three weeks of in vivo anti-IL-10R mAb treatment minimally affected the gB498-505-specific TG resident CD8+ T cells, but did dramatically increase in the number of functional CD8+ T cells specific for subdominant epitopes, and improved control of HSV-1 latency in ex vivo TG cultures. We conclude that CD8+ T cells specific for subdominant epitopes are suppressed in the TG by host secretion of IL-10. Our findings suggest the exciting possibility that rescue from IL-10 suppression will expand the functional repertoire of HSV-specific CD8+ T cells and reduce the likelihood of viral reactivation from latency.
Published Version
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