Levels of regulatory T cells CD69 NKG2D IL-10 are increased in patients with autoimmune thyroid disorders
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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. © 2015, Springer Science Business Media New York.
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Regulatory T (Treg) cells play an important role in the pathogenesis of autoimmune thyroid disorders (AITD). New subsets of CD4%2bCD69%2b and CD4%2bNKG2D%2b 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%2bCD69%2bIL-10%2b, CD4%2bCD69%2bNKG2D%2b, and CD4%2bCD69%2bIL-10%2bNKG2D%2b cells, in peripheral blood from GD patients compared to controls. The increase in CD4%2bCD69%2bIL-10%2b and CD4%2bCD69%2bIL-10%2bNKG2D%2b T cells was especially remarkable in patients with active Graves’ ophthalmopathy (GO), and a significant positive correlation between GO activity and CD4%2bCD69%2bIL-10%2b or CD4%2bCD69%2bIL-10%2bNKG2D%2b 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%2b regulatory T cells subpopulations compared to autologous peripheral blood. The presence of CD69%2b, NKG2D%2b, and IL-10%2b cells was confirmed by immunofluorescence microscopy. In vitro functional assays showed that CD69%2b 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%2b regulatory lymphocytes are increased in AITD patients, but they are apparently unable to down-modulate the autoimmune response and tissue damage. © 2015, Springer Science%2bBusiness Media New York.
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CD69; Graves’ disease; Hashimoto thyroiditis; IL-10; NKG2D; Treg cells CD69 antigen; interleukin 10; natural killer cell receptor NKG2D; CD69 antigen; IL10 protein, human; interleukin 10; KLRK1 protein, human; lectin; leukocyte antigen; natural killer cell lectin like receptor subfamily K; T lymphocyte antigen; adult; Article; autoimmune thyroiditis; CD69 NKG2D IL 10 T lymphocyte; clinical article; controlled study; disease severity; effector cell; endocrine ophthalmopathy; female; flow cytometry; Graves disease; Hashimoto disease; human; human cell; human tissue; immunofluorescence microscopy; in vitro study; lymphocyte activation; male; pathogenesis; phenotype; priority journal; regulatory T lymphocyte; thyroid gland tissue; aged; autoimmune thyroiditis; biosynthesis; cell culture; endocrine ophthalmopathy; goiter; Hashimoto disease; metabolism; middle aged; regulatory T lymphocyte; thyroid gland; ultrastructure; Adult; Aged; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Cells, Cultured; Female; Goiter; Graves Ophthalmopathy; Hashimoto Disease; Humans; Interleukin-10; Lectins, C-Type; Lymphocyte Activation; Male; Middle Aged; NK Cell Lectin-Like Receptor Subfamily K; T-Lymphocytes, Regulatory; Thyroid Gland; Thyroiditis, Autoimmune
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CD69; Graves’ disease; Hashimoto thyroiditis; IL-10; NKG2D; Treg cells CD69 antigen; interleukin 10; natural killer cell receptor NKG2D; CD69 antigen; IL10 protein, human; interleukin 10; KLRK1 protein, human; lectin; leukocyte antigen; natural killer cell lectin like receptor subfamily K; T lymphocyte antigen; adult; Article; autoimmune thyroiditis; CD69+ NKG2D+ IL 10+ T lymphocyte; clinical article; controlled study; disease severity; effector cell; endocrine ophthalmopathy; female; flow cytometry; Graves disease; Hashimoto disease; human; human cell; human tissue; immunofluorescence microscopy; in vitro study; lymphocyte activation; male; pathogenesis; phenotype; priority journal; regulatory T lymphocyte; thyroid gland tissue; aged; autoimmune thyroiditis; biosynthesis; cell culture; endocrine ophthalmopathy; goiter; Hashimoto disease; metabolism; middle aged; regulatory T lymphocyte; thyroid gland; ultrastructure; Adult; Aged; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Cells, Cultured; Female; Goiter; Graves Ophthalmopathy; Hashimoto Disease; Humans; Interleukin-10; Lectins, C-Type; Lymphocyte Activation; Male; Middle Aged; NK Cell Lectin-Like Receptor Subfamily K; T-Lymphocytes, Regulatory; Thyroid Gland; Thyroiditis, Autoimmune
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