The role of natural killer cells in protection of mice against death and corneal scarring following ocular HSV-1 infection

C57BL/6 mice depleted of NK (natural killer) cells with anti-asialo-GM1 ant ibody were more susceptible to lethal HSV-1 ocular challenge (12% survival) than control C57BL/6 mice (100% survival), CD4(+) depleted mice (100% surv ival), CD8(+) depleted mice (80% survival), or macrophage depleted mice (85 % survival). NK depletion also resulted in significantly higher levels of H SV-1 induced corneal scarring than was seen with any of the other groups. C 57BL/6 mice depleted of NK cells with PK136 (anti-NK1.1 antibody which is m ore specific for NK cells than is anti-asialo-GM1 antibody) were also more susceptible to HSV-1 ocular challenge than T cell or macrophage depleted mi ce. Vaccination completely protected NK depleted mice against death and cor neal scarring. In contrast to C57BL/6 mice, in BALB/c mice, NK depletion ha d no effect on survival or corneal scarring following ocular HSV-I challeng e. Experiments with IFN-gamma knockout mice (IFN-gamma(o/o) mice) suggested that IFN-gamma played a minor role in protection of naive mice against dea th following HSV-I challenge. However, IFN-gamma did not appear to be an im portant factor in protection against HSV-1 induced eye disease. Thus, prote ction against HSV-1 induced corneal scarring in naive mice appeared to be d ue to a non-INF-gamma NK function. Our results therefore suggest that NK ce lls were very important in protecting naive C57BL/6 mice but not vaccinated C57BL/6 mice against corneal scarring and death following ocular HSV-1 cha llenge. (C) 2000 Elsevier Science B.V. All rights reserved.