CHARACTERIZATION OF RESISTANCE TO MURINE EXPERIMENTAL AUTOIMMUNE-THYROIDITIS - DURATION AND AFFERENT ACTION OF THYROGLOBULIN-INDUCED AND TSH-INDUCED SUPPRESSION

Genetically susceptible mice develop experimental autoimmune thyroiditis (EAT) after immunization with mouse thyroglobulin (MTg). Earlier studies have shown that resistance to EAT induction can be activated by two regimens, pretreatment with deaggregated MTg (dMTg) or with thyroid-stimulating hormone (TSH). With both protocols, suppression is linked to a ≥2-3 day increase in circulatory MTg level and is mediated by CD4+ suppressor T cells (Ts). To assess the duration of suppression, CBA (H-2k) mice were injected with dMTg or infused with TSH via an osmotic pump for 3-4 days and then challenged with MTg + adjuvant at intervals up to 73 days for dMTg-pretreated mice or up to 94 days for TSH-pretreated mice. Suppression was measurable for at least 73 days after injected dMTg. TSH-induced suppression was also long-lasting; resistance was strong 38 days after TSH infusion and was still measurable on Day 66. The Thy-1+, CD4+ Ts which transfer MTg-induced suppression were further characterized by treatment with IrJ antibodies plus complement prior to transfer. This treatment abolished the transfer of suppression which acts in the afferent phase to interfere with EAT induction. The capacity of Ts to suppress the efferent phase of EAT was assessed in vitro and in vivo. Cells from dMTg-pretreated mice did not block the in vitro proliferative response of MTg-primed cells to MTg, nor did these cells, when left intact in situ, reduce the severity of disease produced by the adoptive transfer of thyroiditogenic cells. Similarly, TSH-induced suppression was ineffective in preventing adoptively transferred EAT. Since suppression, which correlates with a temporary increase of circulatory MTg, occurs only at the afferent phase of active immunization, these findings lend support to our earlier hypotheses that circulatory MTg serves a physiologic role in maintaining normal self-tolerance by sustaining low levels of Ts activation and that additional rise above baseline increases and prolongs resistance to EAT induction. © 1993 Academic Press. All rights reserved.