An Immunologist's View of Herpes Simplex Keratitis: Thygeson Lecture 1996, Presented at the Ocular Microbiology and Immunology Group Meeting, October 26, 1996

被引:0
作者
Hendricks, RL
机构
关键词
herpes simplex virus 1; cytokines; interleukin-2; keratitis; inflammation; cornea; interferon gamma;
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暂无
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose, To review recent progress in understanding the mechanisms of herpes simplex virus 1 (HSV-l)-induced immunopathology in the cornea, as revealed by studies in a mouse model. Methods. The corneas of A/J mice were infected with 5x10(4) 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. 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 or 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 extravastion from the blood in association with reduced platelet endothelial 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. Conclusion. 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 (Thl) cytokines IL-2 and LFN-gamma.
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页码:503 / 506
页数:4
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