Noninvolvement of IL-4 and IL-10 in tolerance induction to experimental autoimmune thyroiditis

The mechanisms of tolerance induced with deaggregated mouse thyroglobulin (dMTg) in experimental autoimmune thyroiditis (EAT) is not yet well defined. As shown previously, the induction and maintenance of tolerance require CD4+ T cells exerting active regulatory function to prevent EAT induction. To examine whether Th2 cells are responsible for resistance we injected anti-IL-4 and anti-IL-10, separately or together, into CBA (H2k) mice at the time of MTg pretreatment to study the role of IL-4 and IL-10 in tolerance induction. Our results show that tolerance can be well established without involving IL-4 or IL-10. To determine whether IL-4 was involved in tolerance induction in another EAT-susceptible strain, IL-4 knockout mice on B10.Q background were similarly pretreated with dMTg and immunized. These IL-4 knockout mice exhibited very good tolerance. The lack of response to EAT induction was not due to IL-4 deficiency, since immunized IL-4 knock-out control mice developed severe EAT. Moreover, resistance was strong in IL-4 knock-out mice also given anti-IL-10. The data in both susceptible strains show that IL-4 and IL-10 play a small role in induced resistance to EAT.