Superiority of thyroid peroxidase DNA over protein immunization in replicating human thyroid autoimmunity in HLA-DRB1*0301 (DR3) transgenic mice
| Autor: | Yi-chi M. Kong, Qiang Wan, J. P. Banga, Monika Gora, Chella S. David, G. Alsharabi, Wei Zen Wei, Alvaro A. Giraldo, Andrzej Gardas, Jeffrey C. Flynn |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
endocrine system
endocrine system diseases medicine.medical_treatment Immunology Thyroid Gland HLA-DR3 Autoimmunity Mice Transgenic medicine.disease_cause Iodide Peroxidase Thyroiditis Autoimmune thyroiditis Epitopes Mice HLA-DR3 Antigen Mice Inbred NOD Thyroid peroxidase Granulocyte Colony-Stimulating Factor medicine Animals Immunology and Allergy Autoantibodies Autoimmune disease biology Thyroid Thyroiditis Autoimmune DNA medicine.disease Interleukin-12 Mice Inbred C57BL medicine.anatomical_structure Models Animal Animal Studies biology.protein Female Immunization Thyroglobulin |
| Zdroj: | Clinical and Experimental Immunology. 137:503-512 |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1111/j.1365-2249.2004.02553.x |
| Popis: | SUMMARYMurine experimental autoimmune thyroiditis (EAT), characterized by thyroid destruction after immunization with thyroglobulin (Tg), has long been a useful model of organ-specific autoimmune disease. More recently, porcine thyroid peroxidase (pTPO) has also been shown to induce thyroiditis, but these results have not been confirmed. When (C57BL/6 × CBA)F1 mice, recently shown to be susceptible to mouse TPO-induced EAT, were immunized with plasmid DNA to human TPO (hTPO) and cytokines IL-12 or GM-CSF, significant antibody (Ab) titres were generated, but minimal thyroiditis was detected in one mouse only from the TPO + GM-CSF immunized group. However, after TPO DNA immunization of HLA-DR3 transgenic class II-deficient NOD mice, thyroiditis was present in 23% of mice injected with TPO + IL-12 or GM-CSF. We also used another marker for assessing the closeness of the model to human thyroid autoimmunity by examining the epitope profile of the anti-TPO Abs to immunodominant determinants on TPO. Remarkably, the majority of the anti-TPO Abs was directed to immunodominant regions A and B, demonstrating the close replication of the model to human autoimmunity. TPO protein immunizations of HLA-DR3 transgenic mice with recombinant hTPO did not result in thyroiditis, nor did immunization of other mice expressing HLA class II transgenes HLA-DR4 or HLA-DQ8, with differential susceptibility to Tg-induced EAT. Moreover, our efforts to duplicate exactly the experimental procedures used with pTPO also failed to induce thyroiditis. The success of hTPO plasmid DNA immunization of DR3+ mice, similar to our reports on Tg-induced thyroiditis and thyrotropin receptor DNA-induced Graves’ hyperthyroidism, underscores the importance of DR3 genes for all three major thyroid antigens, and provides another humanized model to study autoimmune thyroid disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|