The role of natural killer cells in the development of herpes simplex virus type 1 induced stromal keratitis in mice

Abstract

Natural killer (NK) cells and acquired cell-mediated immunity effector cells (delayed type hypersensitivity (DTH) and cytotoxic T lymphocytes (CTL)) have been reported to play a vital role in the defence of the host against tumour and viral infections in locations other than the eye. A vigorous cellular inflammatory response to viral infections of the cornea, however, with the attendant damage to the corneal clarity, has obvious evolutionary disadvantages, and a substantial body of evidence indicates that in animals (e.g. mice) which are highly susceptible to inflammatory destruction of the cornea following corneal encounter with herpes simplex virus, it is the animal's immunological/inflammatory response which is responsible for the corneal damage. We examined the role of natural killer cells in the development of herpes stromal keratitis (HSK) in NK-deficient (C57BL/6J-bgj (beige)) mice and their NK-competent (C57BL/6J (black) relatives. The beige (NK-deficient) mice were just as resistant to HSK as were the black mice. We also studied the effects of NK cell depletion of BALB/c Igh-1 disparate congenic mice. C.AL-20 (Igh-1d) mice are ordinarily highly susceptible to necrotising HSK. In vivo NK-cell depletion in these mice significantly decreased the incidence and severity of HSK in these animals (p < 0.0005). Corneas from untreated C.AL-20 mice contained T cells, macrophages and NK cells. The corneal infiltrate from NK-depleted C.AL-20 mice consisted of T cells and macrophages but no NK cells. These data indicate that NK cells are participants in the development of HSK in the murine model of this disease.

Unforeseen Consequences of IL-12 Expression in the Eye of GFAP-IL12 Transgenic Mice Following Herpes Simplex Virus Type 1 Infection

“…Consequently, inflammatory-inducing events within the cornea resulting in structural modifications or corneal opacification can have devastating consequences to the quality of the visual axis. Relative to HSV-1, neutrophils (Thomas et al, 1997), macrophages (Bauer et al, 2001), Langerhans cells (Hendricks et al, 1992a), natural killer cells (Tamesis et al, 1994), and CD4 1 T lymphocytes (Gangappa et al, 1998) seemingly promote the development of herpetic stromal keratitis, which may be related to the production of IL-2 or IFN-g secreted by these cells (Hendricks et al, 1992b;Tang et al, 1997). In the present study, determining the efficacious or detrimental effects of another cytokine generated during the immune response to ocular HSV-1, IL-12, was undertaken using GFAP-IL12 transgenic mice.…”

CD4+ T cell migration into the cornea is reduced in CXCL9 deficient but not CXCL10 deficient mice following herpes simplex virus type 1 infection

“…NK cells are thought to contribute to stromal keratitis [28], control HSV-1 infection [29,30], and respond to a CXCL10 chemical gradient through the receptor CXCR3 [31]. However, similar numbers of NK cells were found residing in the cornea comparing HSV-1-infected WT (225 ± 70 cells/cornea pair), CXCL9−/− (260 ± 90 cells/cornea pair), and CXCL10−/− (190 ± 90/ cornea pair) mice.…”

Immunological Aspects of Herpetic Stromal Keratitis

“…21 On the other hand, in C.AL-20 mice that are highly susceptible to HSV, NK-cell depletion significantly decreases the incidence and severity of HSK. 22 These observations have suggested that the roles of NK cells in HSK could produce completely different results depending on the circumstances.…”