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 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.
Kang
Bong-Seok
BS
Department of Biochemistry, Molecular Biology and AM-Pointology, Dongguk University College of Oriental Medicine and National Research Laboratory for Glycobiology, Kyungju, Kyungbuk, South Korea.
Chung
Tae-Wook
TW
Moon
Jin-Young
JY
Lim
Jong-Kook
JK
Shon
Yun-Hee
YH
Nam
Kyung-Soo
KS
Kim
Dong-Soo
DS
Jeon
Byung-Hoon
BH
Kim
Cheorl-Ho
CH
D000818:Animals; D000906:Antibodies / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006031:Glycosylation; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D008698:Mesylates; D051379:Mice; D008808:Mice, Inbred CBA; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D013552:Swine; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013954:Thyroglobulin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology* / Q000276:immunology* / Q000473:pathology
D000906:Antibodies; D008698:Mesylates; D007371:Interferon-gamma; D013954:Thyroglobulin; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; C012077:trifluoromethanesulfonic acid