The chondroitin 6-sulfate oligosaccharide chain is a major determinant of the immunopathogenicity of human thyroglobulin in CBA/J(H-2Ak) mice
D'Angelo, Daniela (2008) The chondroitin 6-sulfate oligosaccharide chain is a major determinant of the immunopathogenicity of human thyroglobulin in CBA/J(H-2Ak) mice. [Tesi di dottorato] (Inedito)
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We investigated the influence of the chondroitin 6-sulfate oligosaccharide unit at Ser2750 of hTg on the ability of hTg to induce experimental autoimmune thyroiditis in CBA/J(H-2k) mice, by using purified preparations of chondroitin 6-sulfate-devoid hTg (hTgCS0), chondroitin 6-sulfate-containing hTg (hTgCS), and of the chondroitin 6-sulfate-containing nonapeptide centred upon Ser2730. Immunization with hTgCS was associated with markedly more pronounced infiltration of thyroid wih mononuclear cells, in comparison with hTgCS0, and larger secondary proliferative responses of splenocytes to both kinds of hTg in vitro. Cytokines secreted in the supernatants of splenocyte proliferations were predominantly of the TH1 type. Splenocytes from hTgCS-immunized mice secreted larger amounts of IFN-gamma and IL-2 in response to both kinds of hTg, compared with splenocytes from hTgCS0-immunized mice. The hTgCSgp glycopeptide elicited the production of significant levels of IFN-gamma, GM-CSF, IL-6, TNF-alpha and IL-10, but not of IL-2 and IL-5, both in control and immunized groups. The effects of combined hTgCS0 and hTgCSgp on IFN-gamma and GM-CSF production were additive in hTgCS-immunized mice and synergistic in hTgCS0-immunized mice. Synergistic effects were also noticed with IL-17 production in both groups. The presence of chondroitin sulfate did not influence the sensitization and response to hTg of IL-5-producing cells. In keeping with the latter results, comparable levels of anti-hTg antibodies of the IgG class and IgG1 and IgG2a subclasses were found in both immune groups. Thus, the chondroitin 6-sulfate oligosaccharide unit of hTg deeply affected the immunopathogenicity of hTg in murine EAT, by interfering at possibly more than one level in the differentiation process of TH1 cells in response to hTg.
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