Contribution of virus and immune factors to herpes simplex virus type I-induced corneal pathology.
In vivo T-lymphocyte subpopulation depletion techniques were used to identify the roles of L3T4+ (CD4) and Lyt-2+ (CD8) T-lymphocytes in the pathogenesis of corneal stromal disease induced by two different strains of Herpes simplex virus type 1 (HSV-1). Histologic examination of infected corneas revealed significant differences in the composition of the inflammatory corneal infiltrates induced by the RE and KOS strains of HSV-1. The RE strain induced a predominantly polymorphonuclear leukocyte (PMN) infiltrate, which began approximately 1 week after infection and progressed through day 21. Depletion of CD4 cells before corneal infection with RE HSV-1 greatly reduced the incidence and severity of corneal disease; depletion of CD8 cells had no effect. The strain KOS HSV-1 induced an early PMN infiltrate that became predominantly mononuclear by day 21. Depletion of CD4 cells did not change the incidence or severity of KOS HSV-1-induced corneal stromal disease. The corneal lesions of these mice contained numerous CD8 cells. Depletion of CD8 cells before KOS HSV-1 infection of the cornea moderately reduced the incidence of stromal disease. However, in CD8-depleted mice with the disease, PMNs were the most prevalent infiltrating cells, and the disease appeared identical to that seen in RE HSV-1 infected corneas. Simultaneous depletion of CD4 and CD8 cells before KOS HSV-1 infection eliminated stromal disease. However, when T-cell depletion was discontinued in these mice, stromal disease developed in concert with the appearance of T-cells in the lymphoid organs and corneas. Thus, T-lymphocytes are a necessary component of HSV-1 corneal stromal disease. These results further suggest that RE HSV-1 preferentially activates CD4 cells in the cornea, and KOS HSV-1 preferentially activates CD8 cells in the cornea.
Hendricks
R L
RL
Department of Ophthalmology, University of Illinois, Chicago 60612.
Tumpey
T M
TM
D000818:Animals; D003315:Cornea / Q000473:pathology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007107:Immune System / Q000502:physiology*; D007635:Keratitis, Dendritic / Q000150:complications / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D018139:Simplexvirus / Q000145:classification / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology