Herpes stromal keratitis (HSK) is a prevalent and frequently vision-threatening disease associated with herpes simplex virus type 1 (HSV-1) infection. In mice, HSK progression occurs after viral clearance and requires T cells and neutrophils. One model implicates Th1-like CD4 T cells with cross-reactivity between the HSV-1 protein UL6 and a corneal autoantigen. HSK can be prevented by establishing specific immunological tolerance. However, HSK can also occur in T-cell receptor-transgenic X SCID mice lacking HSV-specific T cells. To study the pathogenesis of HSK in the natural host species, we measured local HSV-specific T-cell responses in HSK corneas removed at transplant surgery (n ‫؍‬ 5) or control corneas (n ‫؍‬ 2). HSV-1 DNA was detected by PCR in two specimens. HSV-specific CD4 T cells were enriched in three of the five HSK specimens and were not detectable in the control specimens. Reactivity with peptide epitopes within the tegument proteins UL21 and UL49 was documented. Responses to HSV-1 UL6 were not detected. Diverse HLA DR and DP alleles restricted these local responses. Most clones secreted gamma interferon, but not interleukin-5, in response to antigen. HSV-specific CD8 cells were also recovered. Some clones had cytotoxic-T-lymphocyte activity. The diverse specificities and HLA-restricting alleles of local virus-specific T cells in HSK are consistent with their contribution to HSK by a proinflammatory effect.Herpes simplex keratitis (HSK) is a common and frequently vision-threatening disease. In the natural human host, interstitial inflammation leading to opacification of the light path occurs in 28 to 40% of persons with herpes simplex virus (HSV) infection of the corneal epithelium. Recovery of live virus from the corneal stroma, in the absence of epithelial ulceration, is uncommon, and antiviral therapy does little to prevent the progression from epithelial to stromal disease. In contrast, corticosteroids and cyclosporin A, compounds with antileukocyte effects, are therapeutic. These clinical observations and murine models have recently been reviewed (21, 37). Despite the lack of spontaneous HSV reactivation in mice, these models partially replicate human HSK in that initial productive viral infection is followed by leukocyte infiltration, virus clearance, and an interval of normal histology. A second phase of leukocyte infiltration and chronic inflammation then occurs in the absence of live virus. Hypotheses developed in these models are addressed here using human corneal specimens.Murine models show that both virus and host factors are involved in the pathogenesis of HSK. Live virus scarification into the cornea is required. Inoculation into the anterior chamber leads to antigen-specific tolerance rather than immunopathology (18, 45). The conclusions from various murine models are widely disparate, however. In the congenic mouse strains C.AL-20 and C.B-17, which differ in susceptibility to HSK, an elegant three-way molecular mimicry has been shown to explain both susceptibility and resistance ...

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Clear grafts and improvements in visual acuity can be obtained after PK in patients with Down syndrome, but consideration must be given to careful postoperative care by health care providers and home support personnel.

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