IFN-gamma and IL-2 are protective in the skin but pathologic in the corneas of HSV-1-infected mice.
HSV type 1 (HSV-1) infection of the mouse cornea results in a tissue-destructive inflammatory reaction in the cornea, but little or no disease in the skin surrounding the eye. Depleting T lymphocytes from mice before HSV-1 corneal infection prevents the corneal inflammation but severely exacerbates the periocular skin lesions. Studies described in this communication investigated the role of T cell cytokines in the corneal and periocular skin disease induced by HSV-1 corneal infection. Mice received weekly i.p. injections of rat mAb specific for IL-2, IL-4, or IFN-gamma beginning 1 day before (day -1) or 6 days after (day +6) corneal infection with the RE strain of HSV-1. The severity of corneal inflammation and the area of periocular skin involvement were measured. Treatment with anti-IFN-gamma or anti-IL-2 significantly reduced the incidence and severity of corneal inflammation. Treatment was equally effective when initiated on day -1 (before T cell activation) or day +6 (after T cell activation but before the initiation of corneal inflammation). Treatment with anti-IL-4 had no effect. The histologic features of corneal inflammation in mock-treated mice included neovascularization, corneal edema, and cellular infiltration. Corneas of anti-IL-2-treated mice that developed inflammation had similar but less severe histologic features. Corneas of anti-IFN-gamma-treated mice that developed inflammation had neovascularization and edema but minimal cellular infiltration. Treatment with anti-IFN-gamma or anti-IL-2 significantly exacerbated periocular skin lesions when initiated at day -1, but not when initiated at day +6. Anti-IL-4 treatment had no effect on skin lesions. Treatment with either anti-IFN-gamma or anti-IL-2, when initiated at day -1, significantly inhibited the delayed-type hypersensitivity response to HSV Ag, but when treatment was begun at day +6 only anti-IFN-gamma significantly inhibited the delayed-type hypersensitivity response. Our findings suggest that IFN-gamma and IL-2 are important elements in both an immunopathologic T-lymphocyte response to HSV-1 Ag in the cornea and a protective T lymphocyte response in the skin.
Hendricks
R L
RL
Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago 60612.
Tumpey
T M
TM
Finnegan
A
A
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D003315:Cornea / Q000382:microbiology / Q000473:pathology; D006684:HLA-DR Antigens; D006561:Herpes Simplex / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D016849:Keratitis, Herpetic / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008805:Mice, Inbred A; D012867:Skin / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma