Immunobiology of Langerhans cells on the ocular surface. II. Role of central corneal Langerhans cells in stromal keratitis following experimental HSV-1 infection in mice.
Stromal keratitis is typically the consequence of infection with herpes simplex virus type 1 (HSV-1). The pathogenesis of this disease remains elusive, although it is generally believed that there is an important immunological component. It has been proposed that stromal keratitis is mediated by virus-specific T lymphocytes of the delayed hypersensitivity type. However, while virtually all individuals infected with HSV-1 develop delayed hypersensitivity, only a small fraction actually develop stromal keratitis. To explain this discrepancy, we reasoned as follows: epidermal Langerhans cells are believed to be crucial to the induction of delayed hypersensitivity; since the cornea normally contains few or no cells of this type, the presence of Langerhans cells in the central corneal epithelium at the time of virus infection might promote the development of stromal keratitis. To test this hypothesis, cautery wounds of central regions of mouse corneas were used to induce migration of Langerhans cells into the corneal epithelium. These mice were then infected with HSV-1 on the ipsilateral snout, an infection that results in zosteriform spread of virus via the trigeminal nerve into the anterior segment of the ipsilateral eye within 3-5 days after inoculation. We found that the eyes of cauterized mice displayed a very high incidence of severe stromal keratitis. By contrast, non-cauterized corneas of control, snout-infected mice displayed much less evidence of stromal disease. Moreover, the rapidity of onset of systemic delayed hypersensitivity to HSV-1 was accelerated in the mice with cauterized corneas, compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
McLeish
W
W
Department of Ophthalmology, University of Miami School of Medicine, FL 33101.
Rubsamen
P
P
Atherton
S S
SS
Streilein
J W
JW
D000818:Animals; D003315:Cornea / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D006968:Hypersensitivity, Delayed; D007635:Keratitis, Dendritic / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018139:Simplexvirus / Q000276:immunology*