Monoclonal antibody to IFN-gamma modifies pulmonary inflammatory responses and abrogates immunity to Schistosoma mansoni in mice vaccinated with attenuated cercariae.
In C57Bl/6 mice vaccinated with a single dose of attenuated cercariae of Schistosoma mansoni, the major site of immune elimination of intact challenge parasites is the lungs. The effector mechanism involves the formation of focal inflammatory responses throughout the pulmonary tissues. These foci are rich in CD4+ T cells, believed to be memory:effector cells of the Th1 type. To investigate the role of IFN-gamma in these inflammatory responses, vaccinated mice were treated with neutralizing mAb. Administration on days 4, 8, 12, and 16 post-challenge, the period over which elimination of challenge parasites takes place in the lungs, gave an average 89.5% abrogation of protective immunity. Analysis of pulmonary cell populations recovered by bronchoalveolar lavage from treated nonimmune mice at day 14 post-challenge revealed a sharp increase in pulmonary eosinophilia, relative to intact vaccinated and challenged animals. The inverse relationship between eosinophilia and protection suggests that eosinophils do not play a vital role in the immune effector mechanism in this model. Pulmonary foci of treated mice were larger, less compact, and of different cellular composition from those of control groups. They contained increased numbers of eosinophils, together with numerous multinucleated giant cells. The effects observed in the anti-IFN-gamma mAb-treated mice, together with the maintenance of MHC class II expression on alveolar macrophages in these animals, could all be explained by the production of IL-4 and other Th2 cytokines. Thus, neutralization of IFN-gamma during challenge responses may shift the Th balance towards domination by the Th2 subset.
Smythies
L E
LE
Department of Biology, University of York, England.
Coulson
P S
PS
Wilson
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal; D004802:Eosinophilia / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma