Abstract
Familial and twin studies in Caucasians have established that the MHC class II allele HLA-DRB1*0301 (DR3) is a strong susceptibility gene in Graves' hyperthyroid disease (GD). To determine if a DR3 transgene could help establish an animal model for GD, we expressed DR3 molecules in class II-knockout NOD mice (H2Ag7-). DR3+g7- mice were given cardiotoxin prior to immunization on weeks 0, 3 and 6 with plasmid DNA encoding human thyrotropin receptor (TSHR). Two groups of mice were also coimmunized with plasmid DNA for IL-4 or GM-CSF. Serial bleeds on weeks 8, 11 and 14 showed that approximately 20% of mice produced thyroid-stimulating antibodies (Abs), and approximately 25% had elevated T4 levels. In particular, a subset displayed both signs of hyperthyroidism, resulting in approximately 30% with some aspect of GD syndrome. Additional mice had thyroid-stimulating blocking Abs and/or TSH-binding inhibitory immunoglobulins, while most mice showed strong labelling of TSHR+ cells by flow cytometry. Interestingly, lymphocytic infiltration with thyroid damage and Abs to mouse thyroglobulin were also noted. Vector controls were uniformly negative. Thus, DR3 transgenic mice can serve as a model for GD, similar to our earlier reports that this allele is permissive for the Hashimoto's thyroiditis model induced with human thyroglobulin.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 35-40 |
| Number of pages | 6 |
| Journal | Clinical and Experimental Immunology |
| Volume | 135 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2004 |
| Externally published | Yes |
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Keywords
- Class II-knockout
- DNA vaccination
- Graves' hyperthyroidism
- HLA-DR3 transgene
- Thyrotropin receptor
ASJC Scopus subject areas
- Immunology
Cite this
Graves' hyperthyroidism and thyroiditis in HLA-DRB1*0301 (DR3) transgenic mice after immunization with thyrotropin receptor DNA. / Flynn, J. C.; Rao, P. V.; Gora, M.; Alsharabi, G.; Wei, W.; Giraldo, A. A.; David, C. S.; Banga, J. P.; Kong, Y. M.
In: Clinical and Experimental Immunology, Vol. 135, No. 1, 01.2004, p. 35-40.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Graves' hyperthyroidism and thyroiditis in HLA-DRB1*0301 (DR3) transgenic mice after immunization with thyrotropin receptor DNA
AU - Flynn, J. C.
AU - Rao, P. V.
AU - Gora, M.
AU - Alsharabi, G.
AU - Wei, W.
AU - Giraldo, A. A.
AU - David, C. S.
AU - Banga, J. P.
AU - Kong, Y. M.
PY - 2004/1
Y1 - 2004/1
N2 - Familial and twin studies in Caucasians have established that the MHC class II allele HLA-DRB1*0301 (DR3) is a strong susceptibility gene in Graves' hyperthyroid disease (GD). To determine if a DR3 transgene could help establish an animal model for GD, we expressed DR3 molecules in class II-knockout NOD mice (H2Ag7-). DR3+g7- mice were given cardiotoxin prior to immunization on weeks 0, 3 and 6 with plasmid DNA encoding human thyrotropin receptor (TSHR). Two groups of mice were also coimmunized with plasmid DNA for IL-4 or GM-CSF. Serial bleeds on weeks 8, 11 and 14 showed that approximately 20% of mice produced thyroid-stimulating antibodies (Abs), and approximately 25% had elevated T4 levels. In particular, a subset displayed both signs of hyperthyroidism, resulting in approximately 30% with some aspect of GD syndrome. Additional mice had thyroid-stimulating blocking Abs and/or TSH-binding inhibitory immunoglobulins, while most mice showed strong labelling of TSHR+ cells by flow cytometry. Interestingly, lymphocytic infiltration with thyroid damage and Abs to mouse thyroglobulin were also noted. Vector controls were uniformly negative. Thus, DR3 transgenic mice can serve as a model for GD, similar to our earlier reports that this allele is permissive for the Hashimoto's thyroiditis model induced with human thyroglobulin.
AB - Familial and twin studies in Caucasians have established that the MHC class II allele HLA-DRB1*0301 (DR3) is a strong susceptibility gene in Graves' hyperthyroid disease (GD). To determine if a DR3 transgene could help establish an animal model for GD, we expressed DR3 molecules in class II-knockout NOD mice (H2Ag7-). DR3+g7- mice were given cardiotoxin prior to immunization on weeks 0, 3 and 6 with plasmid DNA encoding human thyrotropin receptor (TSHR). Two groups of mice were also coimmunized with plasmid DNA for IL-4 or GM-CSF. Serial bleeds on weeks 8, 11 and 14 showed that approximately 20% of mice produced thyroid-stimulating antibodies (Abs), and approximately 25% had elevated T4 levels. In particular, a subset displayed both signs of hyperthyroidism, resulting in approximately 30% with some aspect of GD syndrome. Additional mice had thyroid-stimulating blocking Abs and/or TSH-binding inhibitory immunoglobulins, while most mice showed strong labelling of TSHR+ cells by flow cytometry. Interestingly, lymphocytic infiltration with thyroid damage and Abs to mouse thyroglobulin were also noted. Vector controls were uniformly negative. Thus, DR3 transgenic mice can serve as a model for GD, similar to our earlier reports that this allele is permissive for the Hashimoto's thyroiditis model induced with human thyroglobulin.
KW - Class II-knockout
KW - DNA vaccination
KW - Graves' hyperthyroidism
KW - HLA-DR3 transgene
KW - Thyrotropin receptor
UR - http://www.scopus.com/inward/record.url?scp=0347949514&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0347949514&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2249.2004.02333.x
DO - 10.1111/j.1365-2249.2004.02333.x
M3 - Article
C2 - 14678262
AN - SCOPUS:0347949514
VL - 135
SP - 35
EP - 40
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
SN - 0009-9104
IS - 1
ER -