title: Regulatory T cells in human autoimmune thyroid disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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-beta 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-beta, and CD69 as well as CD69+CD25(bright), CD69+TGF-beta, 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-beta mRNA were found in thyroid tissue, and thyroid cell infiltrates synthesized in vitro significant levels of TGF-beta 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.
authors.affiliation: Departamento de Inmunología, Facultad de Medicina, Universidad Autónoma de San Luis Potosi, Ave. V. Carranza 2405, 78210 San Luis Potosí, S.L.P. México.
authors.forename: Mónica
authors.initials: M
authors.lastname: Marazuela
authors.forename: María A
authors.initials: MA
authors.lastname: García-López
authors.forename: Nicté
authors.initials: N
authors.lastname: Figueroa-Vega
authors.forename: Hortensia
authors.initials: H
authors.lastname: de la Fuente
authors.forename: Brenda
authors.initials: B
authors.lastname: Alvarado-Sánchez
authors.forename: Adriana
authors.initials: A
authors.lastname: Monsiváis-Urenda
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: Roberto
authors.initials: R
authors.lastname: González-Amaro
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D016753:Interleukin-10; D037181:Lectins, C-Type; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D016212:Transforming Growth Factor beta; D000099192:CD69 Antigens; C418974:FOXP3 protein, human; C491405:TNFRSF18 protein, human