Regulatory T cells in Graves' disease

• Published in: Clinical endocrinology (Oxford) 2009-10, Vol.71 (4), p.587-593
• Main Authors: Pan, Deshun, Shin, Young-Ha, Gopalakrishnan, Geetha, Hennessey, James, De Groot, Leslie J.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Graves Disease - immunology; Graves Disease - radiotherapy; Humans; Interleukin-2 Receptor alpha Subunit - metabolism; Interleukin-7 Receptor alpha Subunit - metabolism; Iodine Radioisotopes - therapeutic use; Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Polymerase Chain Reaction; RNA, Messenger - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Thyroid. Thyroid axis (diseases); Vertebrates: endocrinology
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/j.1365-2265.2009.03544.x

Summary Context  Graves’ disease (GD) involves auto‐immunity against thyroid cell antigens, but the reasons for induction of auto‐immunity are uncertain. We wished to determine whether there was a deficiency of regulatory T cells in patients with active GD. Design  Venous blood samples were obtained from patients with GD before and after treatment, and controls, and peripheral blood mononuclear cells were prepared. Patients and measurements  Regulatory T cells were enumerated by Fluorescent Activated Cell sorting (FACS) in nineteen patients with untreated GD, 9 patients 6–8 weeks post RAI therapy, and 30 control subjects. Twenty‐one patients with active GD prior to control of hyperthyroidism, 23 euthyroid controls without known autoimmune thyroid disease, and 10 patients who were euthyroid 6–12 months after RAI treatment were studied for expression of genes found in regulatory T cells by real‐time Polymerase Chain reaction (PCR). Results  Percent distribution of CD4+, CD4+CD25+ and CD4+ CD25+int‐hi CD127+lo regulatory T cells was similar in active GD patients and control subjects. The number of CD25+ and CD4+ CD25+int‐hi CD127+lo cells was similar in GD patients and control subjects, but was lower in recently treated patients. Messenger RNA was prepared from PBMC, and reverse transcribed. Copy DNA abundance was evaluated by Real Time PCR using appropriate primers, for GAPDH (glyceraldehyde phosphate dehydrogenase) as a control housekeeping gene, and 5 genes related to function of regulatory T cells. Message RNA for Gadd45 alpha, Gadd45beta (growth arrest and damage inducible proteins), GITR (glucocorticoid inducible TNF receptor) and CD25 (IL‐2R subunit) was more abundant in patients with active GD than in normal controls, and FoxP3 mRNA level was equal to that in controls. Message RNA levels in patients treated and euthyroid for 6 months were also greater than or equal to values in controls. Conclusion  This study provides evidence that there is no deficit in T regulatory cells during active GD, or during the months post therapy.