INTERLEUKIN-12 ALTERS THE ISOTYPE-RESTRICTED ANTIBODY-RESPONSE OF MICE TO HEN EGG-WHITE LYSOZYME

Protein antigens elicit humoral responses in mice that consist predominantly of IgG1 antibodies, We have now investigated the ability of IL-12, a cytokine reported to augment IgG2a anti-hapten responses through activation of T(h)1 cells, to alter antibody responses to hen eggwhite lysozyme (HEL), The normal response of BALB/c mice to HEL is highly restricted to IgG1 expression and therefore provides an excellent system for determining effects of cytokines on expression of other isotypes, Seven days after immunization, IL-12-treated mice demonstrated greatly elevated HEL-specific IgG2a antibody levels and suppressed IgG1 production, while PBS-treated control mice showed a typical IgG1-restricted response, On day 28, IL-12-treated mice showed heightened serum antibody levels of both isotypes, Delaying cytokine treatment until after the typical IgG1 anti-HEL response had already been established also led to significant elevation of serum IgG2a antibody levels, These effects correlated with increased IFN-gamma production; however, administration of IL-12 plus anti-IFN-gamma had little influence on IgG2a enhancement, although it did relieve the early IgG1 suppression, Furthermore, the differential effects of IL-12 on isotype expression did not correlate with time; in fact, IgG2a enhancement correlated with loss of IgG1 suppression. Our findings indicate that (i) IL-12 reproducibly induces large amounts of IgG2a HEL-specific antibodies in vivo; (ii) it can alter isotype profiles of both primary and secondary responses; and (iii) its effects on humoral immunity are not completely explained by induction of T(h)1 cell-derived IFN-gamma.