TOLERANCE TO THYROGLOBULIN BY ACTIVATING SUPPRESSOR MECHANISMS *

The studies of Vladutiu and Rose demonstrated that the induction of autoimmune thyroiditis with emulsified mouse thyroglobulin ( MTg) in good responder mice is linked to the H-2 complex and requires T cells.l! Subsequent studies in H-2 congenic mice with the same B10 background",& confirmed the H-2 linkage of the gene controlling the immune response to thyroglobulin (the Zr-Tg gene). Similar segregation of good and poor responder strains on Balb/c and C3H backgrounds according :o the H-2 haplotype further solidified the major role of the MHC in autoimmune thyroiditis. Both the H-2 linkage and the need for T cells arc found despite the use with MTg of different adjuvantswhich have included complete Freunds adjuvant (CFA) ,l, * lipopolysaccharide (LPS) ,3 and polyadenylic-polyuridylic acid complex (poly A:U) .4 LPS and poly A:U are both soluble adjuvants and have enabled investigators to study autoimmune responses induced by aqueous, unmodified MTg. Self tolerance or the lack of autoimmunity in genetically susceptible, unimmunized mice cannot be attributed to the absence of antigen, inasmuch as thyroglobulin circulates in ng amounts in the natural Nor can it be attributed to the lack of autoreactive T cells, since we have recently shown that autoreactive T cells exist in good responder mice.fi The presence of MTgreactive T cells was revealed by repeated injections (16 times in four weeks) of syngeneic MTg in the absence of adjuvant. IgG production reached high levels in all animals and 50% showed infiltration of the thyroid by mono-