PMID- 11488633
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20071114
IS  - 0896-8411 (Print)
IS  - 0896-8411 (Linking)
VI  - 17
IP  - 1
DP  - 2001 Aug
TI  - Flexibility of TCR repertoire and permissiveness of HLA-DR3 molecules in 
      experimental autoimmune thyroiditis in nonobese diabetic mice.
PG  - 7-15
AB  - Experimental autoimmune thyroiditis (EAT) is inducible in genetically susceptible 
      mice by immunization with mouse thyroglobulin (mTg). With susceptibility linked 
      to MHC class II, EAT is useful in studying human leukocyte antigen (HLA) 
      associations with Hashimoto's thyroiditis. In non-obese diabetic (NOD) mice, 
      approximately 10% thyroiditis incidence occurs with aging. This potential was 
      exploited to examine the T cell repertoire and HLA association in EAT. Similar to 
      B10.K-Vbeta(c)mice with TCRBV genes reduced by approximately 70%, mTg-immunized 
      NOD-Vbeta(c)mice developed thyroiditis comparable to controls, indicating 
      plasticity of the TCR repertoire for pathogenic epitopes. HLA association was 
      evaluated by introducing HLA-DRA/DRB1*0301 (DR3) transgene into class II-negative 
      NOD mice (Ab(0)/NOD). Previously, this HLA-DR3 transgene rendered EAT-resistant 
      B10.M and Ab(0)mice susceptible to both mTg- and hTg-induced EAT. These results 
      are now confirmed. mTg-induced thyroiditis in DR3+ Ab(0)/NOD mice was comparable 
      to that in NOD and DR3- NOD mice, and the proliferative response was stronger. By 
      comparison, NOD mice were only moderately susceptible to hTg-induced EAT. 
      However, thyroiditis was more severe in DR3+ Ab(0)/NOD than in DR3- NOD mice, 
      with no difference in proliferative response to hTg harbouring heterologous 
      epitopes. The confirmed permissiveness of HLA-DR3 molecules on an NOD background 
      for EAT induction by both mTg and hTg supports the importance of this class II 
      gene implicated in some patient studies.
CI  - Copyright 2001 Academic Press.
FAU - Flynn, J C
AU  - Flynn JC
AD  - Department of Immunology and Microbiology, Wayne State University School of 
      Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA.
FAU - Fuller, B E
AU  - Fuller BE
FAU - Giraldo, A A
AU  - Giraldo AA
FAU - Panos, J C
AU  - Panos JC
FAU - David, C S
AU  - David CS
FAU - Kong, Y C
AU  - Kong YC
LA  - eng
GR  - AI14764/AI/NIAID NIH HHS/United States
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 (HLA-DR3 Antigen)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 9010-34-8 (Thyroglobulin)
SB  - IM
MH  - Animals
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - HLA-DR3 Antigen/*genetics/immunology/*metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Transgenic
MH  - Receptors, Antigen, T-Cell, alpha-beta/genetics/*immunology
MH  - Species Specificity
MH  - Thyroglobulin/immunology
MH  - Thyroiditis, Autoimmune/etiology/genetics/*immunology
MH  - Transgenes/genetics/immunology
EDAT- 2001/08/08 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/08/08 10:00
PHST- 2001/08/08 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/08/08 10:00 [entrez]
AID - S0896-8411(01)90528-1 [pii]
AID - 10.1006/jaut.2001.0528 [doi]
PST - ppublish
SO  - J Autoimmun. 2001 Aug;17(1):7-15. doi: 10.1006/jaut.2001.0528.