Long-term effect of primary immunization on subsequent immune responsiveness.
Specific antigen/adjuvant combinations preferentially induce type 1 or type 2 cytokine responses. For example, BALB/c mice primed with TNP-ovalbumin in complete Freund's adjuvant (TNP-OVA/CFA) produce a type 2-dominated response characterized by the activation of IL-4-secreting cells and the production of IgG1 and IgE anti-TNP antibodies. In contrast, mice primed with TNP conjugated to Brucella abortus (TNP-BA) produce a type 1 response dominated by the secretion of IFN-gamma and IgG2a anti-TNP antibodies. We examined whether treating young mice with these antigen/adjuvant combinations altered the cytokine profile of their subsequent immune responses. Mice immunized with TNP-BA and boosted several months later with TNP-OVA/CFA developed a cytokine and antibody profile similar to the priming rather than boosting antigen. This was also observed in mice immunized with TNP-OVA/CFA and boosted with TNP-BA. Both the ratio of IL-4:IFN-gamma-secreting cells and the isotype of antibodies produced by these mice were altered by primary immunization. Analysis of Con A-responsive cells from these animals showed that long-lived changes in the frequency of T lymphocytes available to secrete type 1 versus type 2 cytokines were induced by strong primary immunogens.
Sacks
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Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Klinman
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DM
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D002004:Brucella Vaccine / Q000276:immunology*; D002003:Brucella abortus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors
D000907:Antibodies, Bacterial; D002004:Brucella Vaccine; D007074:Immunoglobulin G; C038600:trinitrophenyl-ovalbumin; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin