Experimental autoimmune thyroid disease (EAT) can be induced experimentally
in mice following immunization with mouse thyroglobulin (mTg) and the adju
vants lipopolysaccharide (LPS) or complete Freund's adjuvant (CFA). EAT can
also be transferred to naive recipients by CD4(+) T cells from mTg-primed
mice. Here we demonstrate a role for IL-12 in the development of EAT by the
ability of neutralizing antibody to IL-12 to reduce disease severity and b
y the lack of significant levels of thyroid infiltration in IL-12p40-defici
ent mice following immunization with mTg and CFA. A single injection of 300
ng IL-12 at the time of initial immunization with mTg and LPS was able to
increase the degree of thyroid infiltration. These data are all consistent
with EAT being a Th1-mediated disease. Conversely, however, administration
of IL-12 over a prolonged period markedly inhibited the induction of EAT by
mTg and CFA and, if given to recipients, inhibited the transfer of EAT by
mTg-primed lymph node cells. The development of an autoantibody response to
mTg was also inhibited when IL-12 was administered throughout the experime
ntal period, suggesting that sustained exposure to IL-12 can be immunosuppr
essive.