Abstract
Purpose: :
CD4 T cells are integral to the immunopathology of both corneal graft rejection and herpes stromal keratitis (HSK). However, the exact cellular interactions responsible for eliciting CD4 T cell effector functions within the cornea during these disease states remain incompletely understood. The naïve murine contains a structured stratification of antigen-presenting cells with MHC class II+ dendritic cells (DC) anchored within the epithelial basement membrane, MHC class IIlo CD11b+ presumed macrophages in the anterior stroma, and MHC class II- CD11b+ macrophages populating the remainder of the stroma. The goal of the current study is to define and contrast the cellular interactions and architecture within corneas inflamed due to either graft rejection or HSK.
Methods: :
Fluorescence confocal microscopy was used to image full-thickness corneal graft tissue from mice who received syngeneic (Balb/c to Balb/c) or allogeneic (C57B6 to Balb/c) corneal transplants, or whose corneas were scarified and infected with herpes simplex virus type 1 (HSV-1) to induce HSK. In some experiments, transgenic mice that express enhanced green fluorescent protein (EGFP) from the CD11c promoter (pCD11c) were used to visualize pCD11c-active DC.
Results: :
Infiltration of CD4 T cells was observed in corneas with HSK following HSV-1 infection and in rejected corneal allografts. Infiltration of pCD11c-active DC was more dense in rejected corneal allografts than was observed in corneas with HSK. Conversely, corneas inflamed secondary to HSV-1 infection contained substantially more CD11b+ presumed macrophages compared to rejected corneal allografts. Consistent with these findings, CD4 T cells appeared to interact predominantly with CD11b+ macrophages in HSK corneas and with pCD11c-active DC in rejected grafts. Interestingly, MHC class II expression was confined to the epithelial and endothelial layers and was essentially absent from the edematous stroma of rejected corneal grafts.
Conclusions: :
While corneal immunopathology caused by graft rejection and HSK are both mediated principally by CD4 T cells, the cellular interactions and architecture within the cornea of these distinct diseases appear to be quite different. Further understanding of the exact cellular interactions within inflamed corneas may allow development of more effective therapeutic interventions for these blinding pathologies.
Keywords: cornea: basic science • inflammation • immunohistochemistry