Concurrent regeneration of T lymphocytes and susceptibility to HSV-1 corneal stromal disease

Abstract

In these studies, mice were simultaneously depleted of CD4 and CD8 T lymphocytes (T cell-depleted) by weekly intraperitoneal injections of rat monoclonal antibodies specific for L3T4 and Lyt-2 respectively, beginning 1 day before topical corneal infection with KOS herpes simplex virus type 1 (HSV-1). Control mice were mock-depleted by weekly injections of saline. All mice developed dendritic epithelial lesions 2-3 days after infection, which healed within 2 days. Fifty percent of the mock-depleted mice developed severe HSV-1 stromal disease, which began 9-14 days after infection. No skin lesions were observed in mock-depleted mice. In contrast, none of the T cell-depleted mice developed HSV-1 corneal stromal disease through an initial 30 day observation period. These mice did develop severe periocular skin lesions. After 30 days, the T cell-depleted mice were subdivided into two groups. In one group, T cell depletion was continued and the mice remained largely free of stromal disease for an additional 30 days (one of 30 mice developed a mild stromal haze). T cell depletion was discontinued in the second group. During the subsequent 30 days the CD4 and CD8 T cells in their lymph nodes and spleens recovered to approximately 50% of normal, and 43% (13 of 30) of the mice developed severe HSV-1 stromal disease. The skin lesions healed in all T cell-depleted mice between days 30 and 60, even when T cell depletion was maintained. Our findings demonstrate that T cells are both protective (preventing the spread of HSV-1 in the skin) and detrimental (inducing the destruction of the corneal stroma).(ABSTRACT TRUNCATED AT 250 WORDS)