INTRAVENOUS ADMINISTRATION OF DEAGGREGATED MOUSE THYROGLOBULIN SUPPRESSES INDUCTION OF EXPERIMENTAL AUTOIMMUNE-THYROIDITIS AND EXPRESSION OF BOTH T(H)1 AND T(H)2 CYTOKINES

Experimental autoimmune thyroiditis (EAT) can be induced by transfer o f mouse thyroglobulin (MTg) and lipopolysaccharide (LPS)-immunized, MT g-activated spleen cells into syngeneic recipients, Recipients of MTg- activated T cells develop lymphocytic EAT, whereas recipients of cells activated by MTg and anti-IL-2R antibody develop a more severe and hi stologically distinct granulomatous form of EAT, Intravenous administr ation of deaggregated MTg (dMTg) 7 days before and 5 days after the fi rst immunization of donor mice with MTg/LPS suppresses the induction o f both forms of EAT. Thyroid infiltration is significantly decreased i n recipients of effector cells from tolerant donors, MTg-specific T ce ll proliferation is partially suppressed in tolerant mice, Both IgG1 a nd IgG2a subclasses of anti-MTg autoantibodies are markedly inhibited in both tolerant donor mice and in recipients of tolerant spleen cells , Expression of T cell cytokine gene transcripts (IL-2, IFN gamma, IL- 4, IL-10, tumor necrosis factor-alpha and transforming growth factor-b eta) are all decreased in spleen cells of donor mice given dMTg. CD8() T cells were not required for expression of tolerance since depletio n of CD8(+) T cells in vivo before tolerance induction or in vitro bef ore MTg restimulation did not abrogate tolerance induction, Taken toge ther, these results suggest that i.v. administration of dMTg can induc e MTg-specific tolerance in both T(h)1- and T(h)2-like EAT effector ce ll precursors, and therefore prevent induction of adoptively transferr ed EAT.