ANALYSIS OF SUSCEPTIBILITY OF NOD MICE TO SPONTANEOUS AND EXPERIMENTALLY-INDUCED THYROIDITIS

Beside diabetes, non-obese diabetic (NOD) mice develop sporadic lympho id infiltration of the thyroid gland, mimicking Hashimoto's thyroiditi s. We have examined the prevalence of those manifestations in NOD mice , the influence of the major histocompatibility complex (MHC) and the association with autoantibodies. The incidence at 1 year is of 14.3% i n wild-type NOD mice versus 19.6% in congenic NOD.H2(k) mice. The mode rate, but statistically significant difference, based on the analysis of 161 NOD and 169 NOD.H2(k) mice, suggests that MHC genes partially c ontrol spontaneous NOD thyroiditis. Autoantibodies against thyroglobul in (Tg) are mouse specific and their presence correlates closely with thyroiditis. The strong correlation between cellular and humoral anoma lies therefore resembles Hashimoto's thyroiditis. NOD and NOD.H2(k) mi ce actively immunized against Tg develop severe chronic lesions with e pithelium necrosis and interstitial tissue fibrosis. Most interestingl y, those lesions do not regress spontaneously as in CBA/J mice. Parado xically, the response to Tg of lymph node cells from NOD mice is weake r both in proliferation and cytokine production. The defect is most ev ident for interferon-gamma-producing T cells and is reflected in the m arked deficit in IgG2a antibodies. Thus a moderate anti-Tg response se ems to favor chronicity of thyroiditis. In conclusion, NOD and NOD.H2( k) mice offer a unique opportunity of analyzing the factors leading to immune chronicity in a genetic context which promotes autoimmune endo crino-pathies.