Herpes stromal keratitis (HSK) is a devastating problem for which no completely satisfactory therapy exists. The immunopathogenesis of HSK is incompletely understood. We have produced and studied a murine model of HSK and have shown a strong influence of the gene in or closely linked to the Igh immunoglobulin allotype loci on Chromosome 12 on the immune/inflammatory response to herpes encounter n the cornea. The interplay between lymphocyte-mediated and antibody-mediated responses in protection from versus production of inflammatory corneal destruction is complicated, but results from our studies suggest that the critical determinants in mediating the balance between protection as opposed to pathology development revolve around immunoregulatory control which derives from products encoded by the Igh-1 and closely linked genes on Chromosome 12. Our studies lead us to the hypothesis that antibody idiotypic domain differences between anti-herpes simplex antibody responses and/or differences in HSV-specific T cell receptor repertoires in Igh-1 disparate congenic mice result in differences in cell responses, cell recruitment, and development of clinically obvious pathology in the form of keratopathy. We intend to further analyze the phenomenon of Igh- 1 restriction of HSV-mediated ocular pathology to an analysis of the Igh- governed selection of HSV-specific T cell receptor repertoires. We believe that understanding, on a molecular level, the details of immunoregulatory control of the immune response to herpes simplex virus as it is seen in the eye will provide better insight into more specific therapeutic modulation of inappropriate inflammatory responses to HSV.
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| Heiligenhaus, A; Wells, P A; Foster, C S (1995) Immunisation against HSV-1 keratitis with a synthetic gD peptide. Eye (Lond) 9 ( Pt 1):89-95 |
| Tamesis, R R; Messmer, E M; Rice, B A et al. (1994) The role of natural killer cells in the development of herpes simplex virus type 1 induced stromal keratitis in mice. Eye (Lond) 8 ( Pt 3):298-306 |
