Overexpression of interleukin-4 delays virus clearance in mice infected with respiratory syncytial virus.
Although interleukin-4 (IL-4) expression has been implicated in vaccine-enhanced respiratory syncytial virus (RSV) disease, its role in mediating the immune response to primary RSV infection remains unclear. To assess the effect of IL-4 production on typical RSV infection, transgenic mice which either overexpress or fail to express IL-4 were challenged intranasally with RSV and their responses were compared to those of the parent strains. IL-4-deficient mice eliminated virus from the lung as quickly as did C57BL/6 controls. In contrast, mice which constitutively overexpress IL-4 showed delayed virus clearance compared with mice of the FVB/N control strain, although peak viral titers did not differ. IL-4 overexpression increased the magnitude of the subsequent antibody response. Lung lymphocytes harvested from IL-4-overexpressing mice post-RSV challenge showed diminished RSV-specific cytolytic activity compared with controls. Both IL-4-deficient and IL-4-overexpressing strains resisted rechallenge. These data imply that constitutive IL-4 expression delays or suppresses the development of a virus-specific cytotoxic lymphocyte population important in clearing primary RSV infection.
Fischer
J E
JE
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2582, USA.
Johnson
J E
JE
Kuli-Zade
R K
RK
Johnson
T R
TR
Aung
S
S
Parker
R A
RA
Graham
B S
BS
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D015847:Interleukin-4 / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009666:Nose / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014779:Virus Replication
D000914:Antibodies, Viral; D015847:Interleukin-4