TY - JOUR
T1 - Coexpression of susceptible and resistant HLA class II transgenes in murine experimental autoimmune thyroiditis
T2 - DQ8 molecules downregulate DR3-mediated thyroiditis
AU - Flynn, Jeffrey C.
AU - Wan, Qiang
AU - Panos, John C.
AU - McCormick, Daniel J.
AU - Giraldo, Alvaro A.
AU - David, Chella S.
AU - Kong, Yi Chi M.
N1 - Funding Information:
We are grateful to Julie Hanson and her staff for the breeding and care of mice. We are also grateful to Ann Mazurco and Nicole Maples-Vollhardt for their excellent histologic preparation of tissues. We also thank Dr Charles Jeffries for kindly supplying the LPS. This work was supported in part by Grant DK45960 from the National Institute of Diabetes and Digestive and Kidney Diseases and a grant from the St John Hospital and Medical Center (Y. M. Kong), and Grant AI14764 from the National Institute of Allergy and Infectious Diseases (C. S. David) for HLA transgenic mice. Presented in part at the 27th annual meeting of the European Thyroid Association, in Warsaw, Poland, 25–29 August 2001 (J. Endocrinol. Invest., 24(supplement to no. 6):60, 2001).
PY - 2002/5
Y1 - 2002/5
N2 - Experimental autoimmune thyroiditis (EAT) can be induced in genetically susceptible mice by immunization with the self antigen, thyroglobulin (Tg). Since susceptibility is linked to H2 class II molecules, we have generated human leukocyte antigen (HLA) class II transgenic mice to study potential HLA associations with Hashimoto's thyroiditis. DR3 (HLA-DRA/DRB1*0301) and DQ8 (HLA-DQA1*0301/DQB1*0302) transgenes were introduced into class II-negative Ab0/B10 and Ab0 nonobese diabetic (Ab0/NOD) mice. Previous work had shown that DR3 transgenic mice were susceptible to both mouse Tg and human Tg-induced EAT, whereas DQ8 transgenic mice were moderately susceptible only to human Tg induction. In this report, we examined the effect of DQ8 transgene on mouse Tg- and human Tg-induced EAT in double transgenic DR3/DQ8 mice. After mouse Tg induction, thyroiditis in DR3+DQ8+ Ab0/B10 mice was significantly less severe than in DR3+ mice but more severe than in DQ8+ mice. No difference in thyroiditis was observed between DR3+ and DR3+DQ8+ mice in another background strain, Ab0/NOD. However, after immunization with human Tg, DQ8 coexpression downregulated thyroiditis severity, compared to DR3+ mice, whereas thyroiditis was more extensive than in DQ8+ mice. Thus, depending on the background strain and the Tg used to induce disease, the presence of the DQ8 transgene can reduce thyroiditis mediated by DR3 molecules.
AB - Experimental autoimmune thyroiditis (EAT) can be induced in genetically susceptible mice by immunization with the self antigen, thyroglobulin (Tg). Since susceptibility is linked to H2 class II molecules, we have generated human leukocyte antigen (HLA) class II transgenic mice to study potential HLA associations with Hashimoto's thyroiditis. DR3 (HLA-DRA/DRB1*0301) and DQ8 (HLA-DQA1*0301/DQB1*0302) transgenes were introduced into class II-negative Ab0/B10 and Ab0 nonobese diabetic (Ab0/NOD) mice. Previous work had shown that DR3 transgenic mice were susceptible to both mouse Tg and human Tg-induced EAT, whereas DQ8 transgenic mice were moderately susceptible only to human Tg induction. In this report, we examined the effect of DQ8 transgene on mouse Tg- and human Tg-induced EAT in double transgenic DR3/DQ8 mice. After mouse Tg induction, thyroiditis in DR3+DQ8+ Ab0/B10 mice was significantly less severe than in DR3+ mice but more severe than in DQ8+ mice. No difference in thyroiditis was observed between DR3+ and DR3+DQ8+ mice in another background strain, Ab0/NOD. However, after immunization with human Tg, DQ8 coexpression downregulated thyroiditis severity, compared to DR3+ mice, whereas thyroiditis was more extensive than in DQ8+ mice. Thus, depending on the background strain and the Tg used to induce disease, the presence of the DQ8 transgene can reduce thyroiditis mediated by DR3 molecules.
KW - Autoimmune thyroiditis
KW - EAT
KW - HLA-DQ8
KW - HLA-DR3
KW - NOD
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U2 - 10.1006/jaut.2002.0587
DO - 10.1006/jaut.2002.0587
M3 - Article
C2 - 12126634
AN - SCOPUS:0036591231
SN - 0896-8411
VL - 18
SP - 213
EP - 220
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
IS - 3
ER -