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 antibody were more susceptible to lethal HSV-1 ocular challenge (12% survival) than control C57BL/6 mice (100% survival), CD4+ depleted mice (100% survival), CD8+ depleted mice (80% survival), or macrophage depleted mice (85% survival). NK depletion also resulted in significantly higher levels of HSV-1 induced corneal scarring than was seen with any of the other groups. C57BL/6 mice depleted of NK cells with PK136 (anti-NK1.1 antibody which is more 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 mice. Vaccination completely protected NK depleted mice against death and corneal scarring. In contrast to C57BL/6 mice, in BALB/c mice, NK depletion had no effect on survival or corneal scarring following ocular HSV-1 challenge. Experiments with IFN-gamma knockout mice (IFN-gamma(o/o) mice) suggested that IFN-gamma played a minor role in protection of naïve mice against death following HSV-1 challenge. However, IFN-gamma did not appear to be an important factor in protection against HSV-1 induced eye disease. Thus, protection against HSV-1 induced corneal scarring in naive mice appeared to be due to a non-INF-gamma NK function. Our results therefore suggest that NK cells were very important in protecting naive C57BL/6 mice but not vaccinated C57BL/6 mice against corneal scarring and death following ocular HSV-1 challenge.
Ghiasi
H
H
Ophthalmology Research, Cedars-Sinai Burns and Allen Research Institute, Los Angeles, CA 90048, USA. ghiasih@cshs.org
Cai
S
S
Perng
G C
GC
Nesburn
A B
AB
Wechsler
S L
SL
D000818:Animals; D003315:Cornea / Q000473:pathology*; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity; D007371:Interferon-gamma / Q000276:immunology; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D007371:Interferon-gamma