Induction of a TC1-mediated experimental autoimmune thyroiditis by deglycosylated porcine thyroglobulin

Contribution of cytotoxic T lymphocytes (CTL) to experimental autoimmune thyroiditis (EAT) was well defined (Speidel et al., Eur. J. Immunol. 1997, 27, 2391-2399, Ref. 7). The native porcine thyroglobulin (pTg) showed high sensitivity to endo-o-N-acetylglucosaminidase F (Endo F) and its molecular we...

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Published in:Immunopharmacology and immunotoxicology 2004-08, Vol.26 (3), p.355-372
Main Authors: Kang, Bong-Seok, Chung, Tae-Wook, Moon, Jin-Young, Lim, Jong-Kook, Shon, Yun-Hee, Nam, Kyung-Soo, Kim, Dong-Soo, Jeon, Byung-Hoon, Kim, Cheorl-Ho
Format: Article
Language:English
Subjects:
Animals
Antibodies - blood
Disease Models, Animal
Female
Glycosylation
Immunization
Interferon-gamma - biosynthesis
Interferon-gamma - immunology
Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
Mesylates
Mice
Mice, Inbred CBA
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
Swine
T-Lymphocyte Subsets - immunology
T-Lymphocytes, Cytotoxic - immunology
Thyroglobulin - administration & dosage
Thyroglobulin - analogs & derivatives
Thyroglobulin - immunology
Thyroiditis, Autoimmune - etiology
Thyroiditis, Autoimmune - immunology
Thyroiditis, Autoimmune - pathology
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Summary:Contribution of cytotoxic T lymphocytes (CTL) to experimental autoimmune thyroiditis (EAT) was well defined (Speidel et al., Eur. J. Immunol. 1997, 27, 2391-2399, Ref. 7). The native porcine thyroglobulin (pTg) showed high sensitivity to endo-o-N-acetylglucosaminidase F (Endo F) and its molecular weights, corresponding to about 330 kDa as a monomer and 660 kDa as a dimer, were reduced to smaller molecular weight forms by Endo F and trifluoromethanesulfonic acid (TMSF). Deglycosylated porcine Tg (dgpTg) and native pTg were injected i.v. into CBA/J mice, without the aid of adjuvants. Both lymphocytic infiltrations of the thyroid glands and levels of Tg-specific CTL were similar to those found in conventional EAT induced by Tg and adjuvants. In contrast, proliferative responses in native pTg and dgpTg-injected mice could not be detected, and titers of antibodies to pTg and dgpTg were 20 times and 30 times lower than that of pTg and adjuvants, respectively. The EAT-inducer CTL belonged to the CD8+ cell subset and exerted their thyroiditogenic potential through release of IFN-gamma. It was concluded that dgpTg-induced EAT is mediated by type 1 cytotoxic T cells (Tcl). Also, results that EAT induction of the glycosylated pTg (gpTg) was much lower than that of dgpTg, suggested that the abberant and incomplete glycosylation of the thyroglobulin is responsible for the induction of autoimmune thyroiditis.
ISSN:0892-3973
DOI:10.1081/IPH-200026872