title: Levels of regulatory T cells CD69(+)NKG2D(+)IL-10(+) are increased in patients with autoimmune thyroid disorders.
abstract: Regulatory T (Treg) cells play an important role in the pathogenesis of autoimmune thyroid disorders (AITD). New subsets of CD4(+)CD69(+) and CD4(+)NKG2D(+) T lymphocytes that behave as regulatory cells have been recently reported. The role of these immunoregulatory lymphocytes has not been previously explored in AITD. We analyzed by multi-parametric flow cytometry different Treg cell subsets in peripheral blood from 32 patients with AITD and 19 controls, and in thyroid tissue from seven patients. The suppressive activity was measured by an assay of inhibition of lymphocyte activation. We found a significant increased percentage of CD4(+)CD69(+)IL-10(+), CD4(+)CD69(+)NKG2D(+), and CD4(+)CD69(+)IL-10(+)NKG2D(+) cells, in peripheral blood from GD patients compared to controls. The increase in CD4(+)CD69(+)IL-10(+) and CD4(+)CD69(+)IL-10(+)NKG2D(+) T cells was especially remarkable in patients with active Graves' ophthalmopathy (GO), and a significant positive correlation between GO activity and CD4(+)CD69(+)IL-10(+) or CD4(+)CD69(+)IL-10(+)NKG2D(+) cells was also found. In addition, these cells were increased in patients with a more severe and/or prolonged disease. Thyroid from AITD patients showed an increased proportion of CD69(+) regulatory T cells subpopulations compared to autologous peripheral blood. The presence of CD69(+), NKG2D(+), and IL-10(+) cells was confirmed by immunofluorescence microscopy. In vitro functional assays showed that CD69(+) Treg cells exerted an important suppressive effect on the activation of T effector cells in controls, but not in AITD patients. Our findings suggest that the levels of CD69(+) regulatory lymphocytes are increased in AITD patients, but they are apparently unable to down-modulate the autoimmune response and tissue damage.
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, C/Diego de León 62, 28006, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodríguez-Muñoz
authors.affiliation: Department of Immunology, School of Medicine, UASLP, San Luis Potosí, SLP, Mexico.
authors.forename: Marlen
authors.initials: M
authors.lastname: Vitales-Noyola
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, C/Diego de León 62, 28006, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ramos-Levi
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, C/Diego de León 62, 28006, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Serrano-Somavilla
authors.affiliation: Department of Immunology, School of Medicine, UASLP, San Luis Potosí, SLP, Mexico.
authors.forename: Roberto
authors.initials: R
authors.lastname: González-Amaro
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, C/Diego de León 62, 28006, Madrid, Spain. monica.marazuela@salud.madrid.org.
authors.forename: Mónica
authors.initials: M
authors.lastname: Marazuela
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis*; D002478:Cells, Cultured; D005260:Female; D006042:Goiter / Q000378:metabolism; D049970:Graves Ophthalmopathy / Q000378:metabolism; D050031:Hashimoto Disease / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D037181:Lectins, C-Type / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism* / Q000648:ultrastructure; D013961:Thyroid Gland / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000378:metabolism*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016753:Interleukin-10; D037181:Lectins, C-Type; D055655:NK Cell Lectin-Like Receptor Subfamily K; D000099192:CD69 Antigens; C508609:IL10 protein, human; C527085:KLRK1 protein, human
keywords: CD69; Graves’ disease; Hashimoto thyroiditis; IL-10; NKG2D; Treg cells