PMID- 12126634
OWN - NLM
STAT- MEDLINE
DCOM- 20030130
LR  - 20191106
IS  - 0896-8411 (Print)
IS  - 0896-8411 (Linking)
VI  - 18
IP  - 3
DP  - 2002 May
TI  - Coexpression of susceptible and resistant HLA class II transgenes in murine 
      experimental autoimmune thyroiditis: DQ8 molecules downregulate DR3-mediated 
      thyroiditis.
PG  - 213-20
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 
      Ab(0)/B10 and Ab(0) nonobese diabetic (Ab(0)/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(+) Ab(0)/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, Ab(0)/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.
FAU - Flynn, Jeffrey C
AU  - Flynn JC
AD  - Department of Immunology and Microbiology, Wayne State University School of 
      Medicine, Detroit, MI 48201, USA.
FAU - Wan, Qiang
AU  - Wan Q
FAU - Panos, John C
AU  - Panos JC
FAU - McCormick, Daniel J
AU  - McCormick DJ
FAU - Giraldo, Alvaro A
AU  - Giraldo AA
FAU - David, Chella S
AU  - David CS
FAU - Kong, Yi-chi M
AU  - Kong YC
LA  - eng
GR  - DK45960/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
RN  - 0 (Autoantigens)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (HLA-DR3 Antigen)
RN  - 9010-34-8 (Thyroglobulin)
SB  - IM
MH  - Animals
MH  - Autoantigens
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - *Genes, MHC Class II
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DR3 Antigen/*genetics
MH  - Humans
MH  - Immunization
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Transgenic
MH  - Thyroglobulin/immunology
MH  - Thyroiditis, Autoimmune/*genetics/*immunology
EDAT- 2002/07/20 10:00
MHDA- 2003/01/31 04:00
CRDT- 2002/07/20 10:00
PHST- 2002/07/20 10:00 [pubmed]
PHST- 2003/01/31 04:00 [medline]
PHST- 2002/07/20 10:00 [entrez]
AID - S0896841102905871 [pii]
AID - 10.1006/jaut.2002.0587 [doi]
PST - ppublish
SO  - J Autoimmun. 2002 May;18(3):213-20. doi: 10.1006/jaut.2002.0587.