Involvement of LFA-1 and ICAM-1 in the herpetic disease resulting from HSV-1 corneal infection.
Herpes simplex virus type 1 (HSV-1) corneal infection in immunologically normal mice results in a transient epithelial lesion followed in about 2 weeks by a potentially blinding inflammatory response in the corneal stroma, and a mild blepharitis. Similarly infected T cell-deficient mice do not develop corneal stromal inflammation, but exhibit severe periocular skin disease and succumb to viral encephalitis. The role of certain adhesion molecules in both T cell activation, and in the extravasation of inflammatory cells from the blood into inflammatory sites is now being established. These studies investigated the involvement of the adhesion pair LFA-1/ICAM-1 in the disease that results from HSV-1 corneal infection in mice. Treatment of mice with mAb to LFA-1 beginning 1 day before HSV-1 corneal infection resulted in a delay in the onset of stromal inflammation, but ultimately stromal inflammation developed to a normal extent. This treatment also caused a significant exacerbation of periocular skin disease, but did not render mice susceptible to encephalitis. Treatment with mAb to ICAM-1 beginning 1 day before HSV-1 corneal infection caused an acceleration of both stromal inflammation and periocular skin disease, and rendered mice uniformly susceptible to lethal encephalitis. Treatment with either mAb beginning 6 days after HSV-1 corneal infection did not significantly affect the clinical course of herpetic disease. Our findings suggest that LFA-1 may play a role in the early phase of corneal stromal inflammation following HSV-1 corneal infection. Both LFA-1 and ICAM-1 appear to be important for protection of the skin from HSV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)
Dennis
R F
RF
Department of Ophthalmology, Rush-Presbyterian-St Luke's Medical Center, Chicago, IL 60612 USA.
Siemasko
K F
KF
Tang
Q
Q
Hendricks
R L
RL
Finnegan
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003319:Corneal Stroma / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018792:Encephalitis, Viral / Q000276:immunology / Q000473:pathology; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D017193:Skin Diseases, Viral / Q000276:immunology / Q000473:pathology; D014709:Vero Cells
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1