Mice lacking the transcription factor subunit Rel can clear an influenza infection and have functional anti-viral cytotoxic T cells but do not develop an optimal antibody response.
Rel, a haemopoietic cell-restricted member of the NF-kappaB/Rel family of transcription factors, has recently been shown to be important in the function of B and T lymphocytes. In an attempt to understand the role of this protein in the immune response, we examined the ability of Rel(-/-) mice to counter an influenza virus infection. Normal levels of virus-specific cytotoxic T cells induced in Rel(-/-) mice were able to clear virus from the lungs, albeit with somewhat delayed kinetics compared to normal mice. Rel(-/-) mice did, however, display a markedly reduced T cell proliferative response to the virus, and exhibited impaired local and systemic influenza virus-specific antibody responses. This defect was sufficient to result in an inability of vaccinated mice, but not of previously infected mice, to acquire antibody-dependent protective immunity to reinfection with the same virus. These findings establish that during the response to influenza virus, Rel function allows optimal development of humoral immunity, a role that apparently cannot be fulfilled by other NF-kappaB/Rel proteins.
Harling-McNabb
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L
Cooperative Research Centre for Vaccine Technology, Department of Microbiology and Immunology, University of Melbourne, Royal Parade, Parkville, Victoria 3052, Australia.
Deliyannis
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G
Jackson
D C
DC
Gerondakis
S
S
Grigoriadis
G
G
Brown
L E
LE
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000918:Antibody Specificity; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout / Q000821:virology; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D020569:Proto-Oncogene Proteins c-rel / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
D000914:Antibodies, Viral; D020569:Proto-Oncogene Proteins c-rel