The involvement of IL-12 in murine experimentally induced autoimmune thyroid disease

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.