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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.The corneas of A/J mice were infected with 5×104 plaque-forming units (PFU) of the RE strain of HSV-1, and the development of inflammation was assessed by slit-lamp, 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.After corneal infection, 60–70% of mice develop corneal opacity due to leukocytic infiltration, neovascularization, and edema. Polymorpho-nuclear neutrophils (PMN) represent 90% of the infiltrating cells, with numerous CD4+, but few CD8+, T cells present. Depleting CD4+ T cells or Langerhans' cells prevents inflammation from developing. Neutralizing interleukin-2 (IL-2) or interferon gamma (IFN-γ) can prevent inflammation or cause a remission of existing disease. IFN-γ 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-γ production, reduced chemotaxis, and loss of PMN viability in the infected cornea.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-γ.