Synergism between mouse thyroglobulin- and vaccination-induced suppressor mechanisms in murine experimental...

Previous studies have shown that genetically susceptible mice can be rendered resistant to the induction of experimental autoimmune thyroiditis (EAT) by pretreatment with deaggregated mouse thyroglobulin (dMTg). This resistance is mediated by CD4+ suppressor T cells (Ts) which suppress the afferent/inductive phase of EAT. Recent work has also shown that resistance to EAT can be achieved by vaccination with irradiated spleen cells previously primed in vivo with MTg and cultured in vitro with MTg (gamma SC). The gamma SC-induced resistance also inhibits the afferent phase of EAT but is mediated by both CD4+ and CD8+ Ts. To determine if dMTg- and gamma SC-induced suppression can cooperate to prevent EAT, we pretreated mice with suboptimal doses of dMTg and gamma SC before challenge with MTg and adjuvant. Mice receiving dMTg or gamma SC only showed suppressed in vitro response to MTg, but the development of thyroid lesions was unaltered. However, mice given one or two subtolerogenic doses of dMTg followed by gamma SC not only showed suppressed in vitro response to MTg, but also little or no thyroiditis, indicating cooperation between these two mechanisms. The cooperation was not reciprocal since reversing the order, giving gamma SC first followed by dMTg, was not effective in suppressing EAT. Thus, suppressor mechanisms activated by pretreatment with dMTg and gamma SC can act synergistically to suppress EAT induction; the two mechanisms may cooperate in vivo to maintain self-tolerance provided that MTg-specific CD4+ Ts are initially activated.