Thyrotropin-Receptor and Thyroid Peroxidase-Specific T Cell Clones and Their Cytokine Profile in Autoimmune Thyroid Disease1
| Autor: | Yoh Hidaka, G A van Seventer, Ellen M. Palmer, Keyoumars Soltani, Carole Ober, Maria-Elena Fisfalen, Y Sawai, Leslie J. DeGroot, Edwin L. Kaplan |
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| Rok vydání: | 1997 |
| Předmět: |
endocrine system
medicine.medical_specialty endocrine system diseases biology business.industry Endocrinology Diabetes and Metabolism medicine.medical_treatment T cell Biochemistry (medical) Clinical Biochemistry Thyroid T helper cell Biochemistry Epitope Endocrinology medicine.anatomical_structure Cytokine Antigen Thyroid peroxidase Internal medicine biology.protein Medicine Thyroglobulin business |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 82:3655-3663 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | We studied the cytokine profile and the immune responses to thyroid antigens of specific T cell clones (TCC) isolated from patients with Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). Antigen-specific TCC were reactive to thyroid peroxidase (TPO), thyroglobulin (Tg) or human recombinant TSH-receptor extracellular domain (TSH-R), and/or their respective peptides. Of the 43 clones derived from HT patients, 65% were reactive to TPO, and 59% of the 32 clones derived from GD patients were reactive to TSH-R. TPO epitopes 100–119 and 625–644 were recognized by 75% of HT-derived clones, whereas TSH-R epitopes 158–176, 207–222, and 343–362/357–376 were recognized by 85% of GD-derived TCC. The TCC were classified according to their cytokine profile into T helper cell (Th)0 [secreting interleukin (IL)-4, IL-5, interferon (IFN)-γ], Th1 (secreting IFN-γ) and Th2 (secreting IL-4 and/or IL-5). Tumor necrosis factor-β and IL-10 were produced by all subsets. The specific TCC were predominantly Th1-like cells in HT, and were Th0- and Th1-like cells in GD. Fifty three percent of Th0 clones were derived from GD patients and were reactive to TSH-R, whereas 50% of Th1 clones were derived from HT patients and were reactive to TPO or Tg. Most Th2 clones (82%) were reactive to TPO and were established from peripheral blood. All these clones produced IL-5, and 64% produced IL-4 and IL-10. Interestingly, IFN-γ was highly produced by TPO- or Tg-specific clones established from HT thyroid tissue. These results confirm at the clonal level our previous studies regarding T cell epitopes on TPO and TSH-R molecules and support the concept that immunodominant T cell epitopes are located on amino acid residues 100–119 and 625–644 of TPO in HT and amino acid residues 158–176, 207–222 and 343–362/357–376 of TSH-R in GD. Our studies also demonstrate that thyroid-specific T cells can be classified into Th0, Th1, and Th2 subsets. TPO- or Tg-specific clones with Th1 phenotype appear to be involved in the pathogenesis of HT, mediating thyroid tissue destruction, whereas TSH-R clones with Th0 phenotype may induce thyroid-stimulating autoantibodies in GD. |
| Databáze: | OpenAIRE |
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