ON THE ESSENTIAL INVOLVEMENT OF NEUTROPHILS IN THE IMMUNOPATHOLOGIC DISEASE - HERPETIC STROMAL KERATITIS

Corneal infection with herpes simplex virus-1 in immunocompetent mice induces an immunopathologic response termed herpetic stromal keratitis (HSK). The earliest sign of disease is neutrophil infiltration, which lasts for 48 to 72 h and then disappears. However, a secondary neutro phil infiltration, this time more massive, occurs, beginning 8 to 9 da ys postinfection, a time in which HSK becomes clinically evident, The role of neutrophils in HSK expression was investigated by eliminating such cells using a specific mAb (RB6-8C5). In neutrophil-depleted immu nocompetent mice, virus replicated more abundantly, but no effects on HSK expression were observed, possibly because sustained neutropenia c ould not be maintained. However, using a severe combined immunodeficie nt mouse model, in which HSK does not occur unless given adoptive tran sfer of CD4(+) T cells, the effects of neutrophil depletion were more pronounced. There were significantly less incidence and severity of HS K in CD4(+) T cell-reconstituted severe combined immunodeficient mice that were depleted of neutrophils as compared with controls. Neutrophi l-depleted mice displayed moderate to severe periocular skin lesions, progressively became cachetic, and developed signs of encephalitis. Vi rus was recovered at higher titers and for longer periods from eyes of neutrophil-depleted animals. Brain virus titers were also significant ly higher on day 12 postinfection as compared with control animals. Th ese results suggest that herpes simplex virus infection of the cornea rapidly invokes recruitment of neutrophils that may aid in viral clear ance, and that neutrophils directly or indirectly serve as agonists in perpetuating a CD4(+) T cell-mediated inflammatory reaction.