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.