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H. Ghiasi, Y. Osorio, D. Brown, G.–C. Perng, C. Espinoza, K. Mott; CD8+CD25+ T Cells Are Highly Pathogenic in the Cornea of HSV–1 gK–Immunized and HSV–1 Ocularly Infected Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3077.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the role of pre–existing anti–HSV–1 antibody, specifically anti–glycoprotein K (gK), in HSV–1–associated corneal scarring (CS) in mice.
Mice were immunized 1X or 3X with HSV–1 gK or gD, or mock immunized. Three weeks after the final immunization, the mice were ocularly infected with HSV–1 strain McKrae or an engineered HSV that expresses 3 copies of gK (HSV–gK3). The presence of CD4, CD8, CD25, and FoxP3 in the cornea, spleen and thymus of the mice were determined by immunocytochemistry, FACS, and RT–PCR before, during the acute phase of infection, and at day 30 post infection (PI).
By day 30 PI, CD8+CD25– T cells were detectable in the corneas of all mice irrespective of immunization, type of virus, or strain of mouse used and did not correlate with CS. In contrast, during acute infection, there were significantly higher numbers of CD8+CD25+ in the corneas of gK–immunized mice than gD– or mock–immunized mice. The presence of CD8+CD25+ in the cornea during this phase of infection exhibited a highly significant correlation with exacerbation of eye disease. On ocular infection with McKrae virus, the numbers of CD8+CD25+ T cells were lower in the corneas of mice that had been immunized 1X with gK, than those immunized 3X. Infection with HSV–gK3 resulted in considerably lower numbers of CD8+CD25+ T cells in the corneas of gK–immunized mice compared with those observed after infection with wild–type McKrae virus, with CD8+CD25+ T cells being undetectable in the corneas of mice immunized 1X with gK and challenged with HSV–gK3.
These data support the concept that pre–existing antibody to HSV–1 contributes to CS after infection. They further indicate that the presence of CD8+CD25+ (regulatory) T cells in the cornea leads to exacerbation of CS. We suggest a model in which viral gK acts as a viral survival mechanism, blocking the induction of CD8+ in the cornea during the acute phase of infection and thus eluding elimination. In mice with pre–existing anti–gK antibody, the gK–specific antibody binds the viral gK in a dose–dependent manner and masks the sites required for its inhibitory effects on CD8+. Thus, "antigenic masking", independent of MHC class I or any other viral gene(s) in gK–immunized mice, promotes induction of CD8+CD25+ T cells in the cornea of infected mice during the acute phase of HSV–1 ocular infection and exacerbates CS and dermatitis.
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