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 of mouse thyroglobulin (MTg) and lipopolysaccharide (LPS)-immunized, MTg-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 histologically distinct granulomatous form of EAT, Intravenous administration of deaggregated MTg (dMTg) 7 days before and 5 days after the first immunization of donor mice with MTg/LPS suppresses the induction of both forms of EAT. Thyroid infiltration is significantly decreased in recipients of effector cells from tolerant donors, MTg-specific T cell proliferation is partially suppressed in tolerant mice, Both IgG1 and 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-beta) are all decreased in spleen cells of donor mice given dMTg. CD8(+) T cells were not required for expression of tolerance since depletion of CD8(+) T cells in vivo before tolerance induction or in vitro before MTg restimulation did not abrogate tolerance induction, Taken together, these results suggest that i.v. administration of dMTg can induce MTg-specific tolerance in both T(h)1- and T(h)2-like EAT effector cell precursors, and therefore prevent induction of adoptively transferred EAT.