This Article Full Text Full Text (PDF) All Versions of this Article: 91/9/3639    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart 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 Marazuela, M. Articles by González-Amaro, R. Search for Related Content PubMed PubMed Citation Articles by Marazuela, M. Articles by González-Amaro, R. Pubmed/NCBI databases Substance via MeSH Related Collections Thyroid Autoimmunity

Regulatory T Cells in Human Autoimmune Thyroid Disease

Servicios de Endocrinología (M.M., M.A.G.-L.) e Inmunología (H.d.l.F., F.S.-M.), Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; and Departamento de Inmunología (N.F.-V., B.A.-S., A.M.-U., R.G.-A.), Facultad de Medicina, Universidad Autónoma de San Luis Potosí, 78210 San Luis Potosí S.L.P., México

Address all correspondence and requests for reprints to: Roberto González-Amaro, M.D., Ph.D., Departamento de Inmunología, Facultad de Medicina, Universidad Autónoma de San Luis Potosi, Ave. V. Carranza 2405, 78210 San Luis Potosí, S.L.P. México. E-mail: rgonzale{at}uaslp.mx.

Context: T regulatory cells have a key role in the pathogenesis of autoimmune diseases in different animal models. However, less information is available regarding these cells in human autoimmune thyroid diseases (AITD).

Objective: The objective of the study was to analyze different regulatory T cell subsets in patients with AITD.

Design: We studied by flow cytometry and immunohistochemistry different T regulatory cell subsets in peripheral blood mononuclear cells (PBMCs) and thyroid cell infiltrates from 20 patients with AITD. In addition, the function of T_REG lymphocytes was assessed by cell proliferation assays. Finally, TGF-ß mRNA in thyroid tissue and its in vitro synthesis by thyroid mononuclear cells (TMCs) was determined by RNase protection assay and quantitative PCR.

Results: PBMCs from AITD patients showed an increased percent of CD4+ lymphocytes expressing glucocorticoid-induced TNF receptor (GITR), Foxp3, IL-10, TGF-ß, and CD69 as well as CD69+CD25^bright, CD69+TGF-ß, and CD69+IL-10+ cells, compared with controls. TMCs from these patients showed an increased proportion of CD4+GITR+, CD4+CD69+, and CD69+ cells expressing CD25^bright, GITR, and Foxp3, compared with autologous PBMCs. Furthermore, a prominent infiltration of thyroid tissue by CD69+, CD25+, and GITR+ cells, with moderate levels of Foxp3+ lymphocytes, was observed. The suppressive function of peripheral blood T_REG cells was defective in AITD patients. Finally, increased levels of TGF-ß mRNA were found in thyroid tissue, and thyroid cell infiltrates synthesized in vitro significant levels of TGF-ß upon stimulation through CD69.

Conclusions: Although T regulatory cells are abundant in inflamed thyroid tissue, they are apparently unable, in most cases, to downmodulate the autoimmune response and the tissue damage seen in AITD.

This article has been cited by other articles:

				M. S. Wilson, J. T. Pesce, T. R. Ramalingam, R. W. Thompson, A. Cheever, and T. A. Wynn Suppression of Murine Allergic Airway Disease by IL-2:Anti-IL-2 Monoclonal Antibody-Induced Regulatory T Cells J. Immunol., November 15, 2008; 181(10): 6942 - 6954. [Abstract] [Full Text] [PDF]

				O. Saitoh, N. Abiru, M. Nakahara, and Y. Nagayama CD8+CD122+ T Cells, a Newly Identified Regulatory T Subset, Negatively Regulate Graves' Hyperthyroidism in a Murine Model Endocrinology, December 1, 2007; 148(12): 6040 - 6046. [Abstract] [Full Text] [PDF]

				S. M. McLachlan, Y. Nagayama, P. N. Pichurin, Y. Mizutori, C.-R. Chen, A. Misharin, H. A. Aliesky, and B. Rapoport The Link between Graves' Disease and Hashimoto's Thyroiditis: A Role for Regulatory T Cells Endocrinology, December 1, 2007; 148(12): 5724 - 5733. [Abstract] [Full Text] [PDF]

				M. Sasaki, H. Ikeda, S. Sawada, Y. Sato, and Y. Nakanuma Naturally-occurring regulatory T cells are increased in inflamed portal tracts with cholangiopathy in primary biliary cirrhosis J. Clin. Pathol., October 1, 2007; 60(10): 1102 - 1107. [Abstract] [Full Text] [PDF]

				M. Bakrac, V. Jurisic, T. Kostic, V. Popovic, S. Pekic, N. Kraguljac, and M. Colovic Pure red cell aplasia associated with type I autoimmune polyglandular syndrome--successful response to treatment with mycophenolate mofetil: case report and review of literature J. Clin. Pathol., June 1, 2007; 60(6): 717 - 720. [Full Text] [PDF]