Jm. Buchanan et al., INTERLEUKIN-12 ALTERS THE ISOTYPE-RESTRICTED ANTIBODY-RESPONSE OF MICE TO HEN EGG-WHITE LYSOZYME, International immunology, 7(9), 1995, pp. 1519-1528
Protein antigens elicit humoral responses in mice that consist predomi
nantly 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 eggwhit
e lysozyme (HEL), The normal response of BALB/c mice to HEL is highly
restricted to IgG1 expression and therefore provides an excellent syst
em for determining effects of cytokines on expression of other isotype
s, Seven days after immunization, IL-12-treated mice demonstrated grea
tly elevated HEL-specific IgG2a antibody levels and suppressed IgG1 pr
oduction, while PBS-treated control mice showed a typical IgG1-restric
ted response, On day 28, IL-12-treated mice showed heightened serum an
tibody levels of both isotypes, Delaying cytokine treatment until afte
r the typical IgG1 anti-HEL response had already been established also
led to significant elevation of serum IgG2a antibody levels, These ef
fects correlated with increased IFN-gamma production; however, adminis
tration of IL-12 plus anti-IFN-gamma had little influence on IgG2a enh
ancement, although it did relieve the early IgG1 suppression, Furtherm
ore, the differential effects of IL-12 on isotype expression did not c
orrelate with time; in fact, IgG2a enhancement correlated with loss of
IgG1 suppression. Our findings indicate that (i) IL-12 reproducibly i
nduces large amounts of IgG2a HEL-specific antibodies in vivo; (ii) it
can alter isotype profiles of both primary and secondary responses; a
nd (iii) its effects on humoral immunity are not completely explained
by induction of T(h)1 cell-derived IFN-gamma.