Inhibition of primary and recall allergen-specific T helper cell type 2-mediated responses by a T helper cell type 1 stimulus.
Allergic responses are characterized by the production of Ag-specific IgE Abs that are dependent upon Th2-mediated T cell help. We determined whether heat-killed Brucella abortus (BA), an inducer of Th1 responses, could influence the allergic Th2-mediated IgE response to OVA adsorbed to alum (O/A). BA plus O/A, but not O/A alone, induced high levels of mRNA for IFN-gamma and IL-12 promptly after injection. Furthermore, initial treatment with BA plus O/A rendered both BALB/c and C57Bl/6 mice incapable of mounting high IgE responses even after repeated challenges with allergen alone. Long term abrogation of anti-OVA IgE correlated with an increased frequency of IFN-gamma-secreting OVA-specific cells and a decreased frequency of IL-4-secreting OVA-specific cells. Initial treatment with anti-IL-12 prevented BA-induced early IFN-gamma production and secondary IgG2a responses, but did not abrogate IgE suppression. Additionally, secondary OVA-specific IgE responses were down-regulated by BA conjugated to OVA or by BA given with O/A. BA-induced down-regulation of secondary IgE responses was associated with increased frequency of Ag-specific IFN-gamma-secreting cells. These results suggest the possibility that even recall Th2-mediated immune responses can be attenuated if Ag is given with a carrier or adjuvant that induces potent Th1-promoting cytokines.
Scott
D E
DE
Center for Biologics Evaluation and Research, Division of Hematology, Food and Drug Administration, Bethesda, MD 20892, USA.
Agranovich
I
I
Inman
J
J
Gober
M
M
Golding
B
B
D000485:Allergens / Q000276:immunology*; D000818:Animals; D002003:Brucella abortus / Q000276:immunology*; D002450:Cell Communication; D005260:Female; D007111:Immunity, Cellular; D007073:Immunoglobulin E / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D007073:Immunoglobulin E