title: Intravenous administration of deaggregated mouse thyroglobulin suppresses induction of experimental autoimmune thyroiditis and expression of both Th1 and Th2 cytokines.
abstract: 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 re-stimulation did not abrogate tolerance induction. Taken together, these results suggest that i.v. administration of dMTg can induce MTg-specific tolerance in both Th1- and Th2-like EAT effector cell precursors, and therefore prevent induction of adoptively transferred EAT.
authors.affiliation: Department of Medicine, University of Missouri School of Medicine, Columbia 65212, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tang
authors.forename: H
authors.initials: H
authors.lastname: Braley-Mullen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006099:Granuloma / Q000276:immunology / Q000517:prevention & control; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007275:Injections, Intravenous; D051379:Mice; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism*; D013954:Thyroglobulin / Q000008:administration & dosage*; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D013954:Thyroglobulin