| Herpes simplex virus (HSV) infection of the cornea may lead to a blinding immunoinflammatory lesion, herpetic stromal keratitis (HSK) in susceptible mice strains. A number of mechanisms have been proposed towards the understanding of the pathogenic mechanisms involved in the lesion pathogenesis. This study is directed at addressing the role of three principal mechanisms: viral antigen hypothesis, molecular mimicry hypothesis and the bystander activation hypothesis. Viral antigens appear to be the initiators of the immune reaction but unlikely to the sole driving mechanism. Extensive evaluation failed to support a role for UL6 peptide from HSV or the IgG2a peptide of IgHb as molecular mimics or autoantigens. Finally, bystander activation was demonstrated as an exclusive means of immunopathology in two different TCR transgenic mice as well as contributing to the lesions in immunocompetent mice during peak clinical stages of the keratitis. This study furthers the mechanistic understanding of lesion pathogenesis and provides insights for future management of HSK. |
