Involvement of CD8⁺T-cells in exacerbation of corneal scarring in mice

Abstract

We have shown that gK vaccination causes an overall increase in T cells and macrophages in the cornea after ocular HSV-1 challenge. The immunopathology induced by gK vaccination appears to be related to CD8+ T-cell activity, as depletion of these cells, but not other immune cells, reduced corneal scarring.

A Recombinant Herpes Simplex Virus Type 1 Expressing Two Additional Copies of gK Is More Pathogenic than Wild-Type Virus in Two Different Strains of Mice

“…Vaccination with gK also appears to block viral clearance from the trigeminal ganglia, which results in a chronic, productive infection (15). We also found that the exacerbation of CS in the gK-immunized mice was due to the presence of CD8 ϩ T cells in the cornea of ocularly infected mice (44). The depletion of CD8 ϩ T cells, but not the depletion of CD4 ϩ T cells or macrophages, reduced the severity of the eye disease to the level detected in mock-immunized or ocularly infected mice.…”

“…Furthermore, we have previously shown that the CS exacerbation in gK-immunized mice correlates with CD8 ؉ T cells, but not with CD4 ؉ T cells or macrophages (44). Recently, it was shown that CD8 ϩ T cells mediate transient herpes stromal keratitis in CD4-deficient mice (33), and that CD8 ϩ T cells are also actively involved in autoimmune diseases (27,41,45,50).…”

“…The depletion of CD8 ϩ T cells, but not the depletion of CD4 ϩ T cells or macrophages, reduced the severity of the eye disease to the level detected in mock-immunized or ocularly infected mice. Of many different protein antigens tested in conjunction with Freund's adjuvant, gK was the only antigen that induced a CD8 ϩ T-cell response in the cornea of ocularly infected mice (44). To help define the effect of gK on HSV-1 pathogenesis, we constructed a recombinant HSV-1 virus that expresses two additional copies of the HSV-1 gK gene, each under the control of the LAT promoter.…”

“…Six-week-old female BALB/c or C57BL/6 mice were infected with 2 ϫ 10 5 PFU/eye of HSV-gK 3 or McKrae virus. It should be noted that C57BL/6 mice are less sensitive than BALB/c mice to infection with McKrae virus (44), but they can be sensitized to infection by immunization with gK (44). Corneas and TG from each infected mouse were collected 5 days postocular infection, and the total RNA was isolated as described in Materials and Methods.…”

“…This exacerbated CS and facial dermatitis was due to the presence of CD8 ϩ T cells in the cornea of ocularly infected mice (44). Furthermore, we have shown that the overexpression of gK in gK-transformed cells causes a collapse of the Golgi apparatus into the endoplasmic reticulum, which inhibits virion egress, glycoprotein transport, and virus-induced cell fusion (10).…”