This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fisfalen, M. E. Articles by DeGroot, L. J. Search for Related Content PubMed PubMed Citation Articles by Fisfalen, M. E. Articles by DeGroot, L. J.

Thyrotropin-Receptor and Thyroid Peroxidase-Specific T Cell Clones and Their Cytokine Profile in Autoimmune Thyroid Disease¹

Department of Medicine (M.E.F., K.S., Y.S., Y.H., L.J.DeG.), Department of Pathology (E.M.P., G.A.vanS.), Department of Surgery (E.K.), and Center for Medical Genetics (C.O.), The University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: Leslie J. DeGroot, 5841 South Maryland, MC 3090, Chicago, Illinois 60637.

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)-], Th1 (secreting IFN-) and Th2 (secreting IL-4 and/or IL-5). Tumor necrosis factor-ß 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- 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.

This article has been cited by other articles:

				H. Inaba, W. Martin, A. S. De Groot, S. Qin, and L. J. De Groot Thyrotropin Receptor Epitopes and Their Relation to Histocompatibility Leukocyte Antigen-DR Molecules in Graves' Disease J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2286 - 2294. [Abstract] [Full Text] [PDF]

				J. Guo, S. M. McLachlan, P. N. Pichurin, C.-R. Chen, N. Pham, H. A. Aliesky, C. S. David, and B. Rapoport Relationship between Thyroid Peroxidase T Cell Epitope Restriction and Antibody Recognition of the Autoantibody Immunodominant Region in Human Leukocyte Antigen DR3 Transgenic Mice Endocrinology, November 1, 2005; 146(11): 4961 - 4967. [Abstract] [Full Text] [PDF]

				J. Guo, P. N. Pichurin, J. C. Morris, B. Rapoport, and S. M. McLachlan "Naked" Deoxyribonucleic Acid Vaccination Induces Recognition of Diverse Thyroid Peroxidase T Cell Epitopes Endocrinology, August 1, 2004; 145(8): 3671 - 3678. [Abstract] [Full Text] [PDF]

				V. Vella, R. Mineo, F. Frasca, E. Mazzon, G. Pandini, R. Vigneri, and A. Belfiore Interleukin-4 Stimulates Papillary Thyroid Cancer Cell Survival: Implications in Patients with Thyroid Cancer and Concomitant Graves' Disease J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2880 - 2889. [Abstract] [Full Text] [PDF]

				Y. Sawai and L. J. DeGroot Binding of Human Thyrotropin Receptor Peptides to a Graves' Disease-Predisposing Human Leukocyte Antigen Class II Molecule J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1176 - 1179. [Abstract] [Full Text]

				J. P. Aniszewski, R. W. Valyasevi, and R. S. Bahn Relationship between Disease Duration and Predominant Orbital T Cell Subset in Graves' Ophthalmopathy J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 776 - 780. [Abstract] [Full Text]

				Y. Ashhab, O. Dominguez, M. Sospedra, C. Roura-Mir, A. Lucas-Martín, and R. Pujol-Borrell A One-Tube Polymerase Chain Reaction Protocol Demonstrates CC Chemokine Overexpression in Graves' Disease Glands J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2873 - 2882. [Abstract] [Full Text]

				B. Rapoport, G. D. Chazenbalk, J. C. Jaume, and S. M. McLachlan The Thyrotropin (TSH)-Releasing Hormone Receptor: Interaction with TSH and Autoantibodies Endocr. Rev., December 1, 1998; 19(6): 673 - 716. [Abstract] [Full Text]