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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006008-08
Application #
3261920
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1985-07-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
02114
Pedroza-Seres, M; Goei, S; Merayo-Lloves, J et al. (1995) T cell receptor V beta gene expression in experimental herpes stromal keratitis. Eye (Lond) 9 ( Pt 5):599-604
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