Resistance to herpetic stromal keratitis in immunized B-cell-deficient mice.
This study evaluates the role of antibody as an indicator of immunity to ocular challenge with herpes simplex virus (HSV). Two genotypes of mice, BALB/c or BALB/c with mu-chain knockout (muK/O; which lack functional B cells), were immunized systemically either with nonvirulent infectious virus or with a eukaryotic expression plasmid encoding glycoprotein B (gB). Whereas naive muK/O mice were 10- to 100-fold more susceptible to HSV infection than BALB/c mice, following immunization both groups showed similar levels of resistance to ocular challenge. Thus both HSV-immunized groups cleared virus within 3 days and showed no signs of ocular lesions. gB DNA-immunized mice cleared virus less rapidly (5 days), and the incidence of lesions was 10 and 25% in BALB/c and muK/O mice, respectively. Since muK/O mice failed to produce detectable anti-HSV antibody, the mechanism of rapid viral removal was assumed to have a T cell basis. However, T cells would likely not mediate any protection directly since such cells were absent in infected corneas during clearance. A likely mechanism of immunity could involve innate defenses, perhaps enhanced by the action of cytokines released from antigen-reactive CD4+ cells in vascularized tissue adjacent to the cornea. Thus an abrupt inflammatory response consisting principally of neutrophils occurred in the corneal stroma in immune mice, and this subsided when virus disappeared. These data reveal that even though the deficiency in generating antibody renders mice more susceptible to HSV infection, once primed, resistance to disease expression is mediated solely by the cellular components and their products.
Daheshia
M
M
Department of Microbiology, The University of Tennessee, M409 Walters Life Sciences Building, Knoxville, Tennessee, 37996-0845, USA.
Deshpande
S
S
Chun
S
S
Kuklin
N A
NA
Rouse
B T
BT
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D003315:Cornea / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007113:Immunity, Innate; D016849:Keratitis, Herpetic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017154:Stromal Cells / Q000276:immunology