An immunologist's view of herpes simplex keratitis: Thygeson Lecture 1996, presented at the Ocular Microbiology and Immunology Group meeting, October 26, 1996.
OBJECTIVE
To review recent progress in understanding the mechanisms of herpes simplex virus 1 (HSV-1)-induced immunopathology in the cornea, as revealed by studies in a mouse model.


METHODS
The corneas of A/J mice were infected with 5 x 10(4) plaque-forming units (PFU) of the RE strain of HSV-1, and the development of inflammation was assessed by slitlamp, histologic, or immunohistochemical examination. The immunopathologic mechanisms were then defined by observing the effect of in vivo depletion of corneal Langerhans' cells, or T-lymphocyte subpopulations, or in vivo neutralization of cytokines on adhesion molecule expression or leukocytic infiltration of the infected cornea.


RESULTS
After corneal infection, 60-70% of mice develop corneal opacity due to leukocytic infiltration, neovascularization, and edema. Polymorphonuclear neutrophils (PMN) represent 90% of the infiltrating cells, with numerous CD4+, but few CD8+, T cells present. Depleting CD4+ T cells of Langerhans' cells prevents inflammation from developing. Neutralizing interleukin-2 (IL-2) or interferon gamma (IFN-gamma) can prevent inflammation or cause a remission of existing disease. IFN-gamma neutralization causes a rapid block of PMN extravasation from the blood in association with reduced platelet endothelial cell adhesion molecule 1 (PECAM-1) expression on the corneal vascular endothelium. IL-2 neutralization results in decreased IFN-gamma production, reduced chemotaxis, and loss of PMN viability in the infected cornea.


CONCLUSIONS
Herpes stromal keratitis is a CD4+ T cell-dependent inflammatory process in which PMN infiltration and destruction of the cornea are regulated, at least in part, by the T-helper type 1 (Th1) cytokines IL-2 and IFN-gamma.
Hendricks
R L
RL
Department of Ophthalmology, University of Illinois at Chicago 60612, USA.
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002465:Cell Movement; D003315:Cornea / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D012189:Retrospective Studies; D012955:Societies, Medical; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000956:Antigens, Viral; D016207:Cytokines; D007371:Interferon-gamma