CD4(+) and CD8(+) cells are key participants in the development of recurrent herpetic stromal keratitis in mice.
Ocular herpes simplex virus (HSV) infection results in an immune-mediated inflammation of the corneal stroma known as herpetic stromal keratitis (HSK). Recurrent HSK is a common cause of virus-induced corneal blindness in humans. The role of CD4(+) and CD8(+) T cell subsets in the disease pathogenesis is ill defined and varies with the virus strain and host genetic background. To examine the contribution of T cell subsets to corneal disease, we studied the development of recurrent HSK in CD4 or CD8 gene knockout (KO) mice ocularly infected with HSV-1 McKrae strain. Following UV-B induced viral reactivation, corneal opacity in latently infected BALB/c (HSV sensitive) CD4 and CD8 KO mice was reduced compared to infected BALB/c mice with normal genotype. In contrast, opacity in C57BL/6 (HSV resistant) CD4 and CD8 KO latent mice did not differ from genetically normal latent mice. Virus-induced corneal opacity was not demonstrable in C57BL/6 CD4/CD8 double KO mice. Increased viral shedding, measured by reactivation rate, days shedding or viral titers, occurred in CD4 KO mice of both strains. Our findings indicate that both CD4(+) and CD8(+) cells play a role in the immunopathogenesis of recurrent HSK, and their role is dependent upon the host genetic profile.
Washington University School Medicine, Department of Ophthalmology and Visual Sciences, Box 8096, 660 S. Euclid, St. Louis, MO, 63110, US. keadle@vision.wustl.edu
T L
TL
Keadle
J L
JL
Morris
J S
JS
Pepose
P M
PM
Stuart
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002522:Chlorocebus aethiops; D003316:Corneal Diseases / Q000276:immunology; D004195:Disease Models, Animal; D018259:Herpesvirus 1, Human / Q000235:genetics; D016849:Keratitis, Herpetic / Q000235:genetics / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014709:Vero Cells
D016827:CD8 Antigens