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Submitted on October 25, 2005
Accepted on June 19, 2006
from Servicios de Endocrinología e Inmunología, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain, and Departamento de Inmunología, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P., México
* To whom correspondence should be addressed. 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: 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 (PBMC) and thyroid cell infiltrates (TMC) from 20 patients with AITD. In addition, the function of TREG lymphocytes was assessed by cell proliferation assays. Finally, TGF-
mRNA in thyroid tissue and its in vitro synthesis by TMNC was determined by Rnase protection assay and quantitative PCR.
Results: PBMC from AITD patients showed an increased percent of CD4+ lymphocytes expressing GITR, Foxp3, IL-10, TGF- and CD69 as well as of CD69+CD25bright, CD69+TGF-, and CD69+IL-10+ cells compared with controls. TMNC from these patients showed an increased proportion of CD4+GITR+, CD4+CD69+, and CD69+ cells expressing CD25bright, GITR and Foxp3 compared with autologous PBMC. 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 TREG cells was defective in AITD patients. Finally, increased levels of TGF- mRNA were found in thyroid tissue, and TMC synthesized in vitro significant levels of TGF- upon stimulation through CD69.
Conclusions: Although T regulatory cells are abundant in inflamed thyroid tissue they are apparently unable, in most cases, to down-modulate the autoimmune response and the tissue damage seen in AITD.
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