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Levels of regulatory T cells CD69+NKG2D+IL-10+ are increased in patients with autoimmune thyroid disorders

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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.

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Conflict of interest

The authors declare no conflict of interest.

Funding

This work has received the following Grants: Proyectos de Investigación en Salud (FIS) PI13-01414, PIE-0041 (funded by Instituto de Salud Carlos III) and S2011/BMD-2328 TIRONET (funded by Comunidad de Madrid) (to Mónica Marazuela). Ayuda Predoctoral de Formación en Investigación en Salud (PFIS) FI11/00668 (funded by Instituto de Salud Carlos III) (to Ana Rodríguez-Muñoz).

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  1. 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

    Ana Rodríguez-Muñoz, Ana Ramos-Levi, Ana Serrano-Somavilla & Mónica Marazuela

  2. Department of Immunology, School of Medicine, UASLP, San Luis Potosí, SLP, Mexico

    Marlen Vitales-Noyola & Roberto González-Amaro

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  1. Ana Rodríguez-Muñoz
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  5. Roberto González-Amaro
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Correspondence to Mónica Marazuela.

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Rodríguez-Muñoz, A., Vitales-Noyola, M., Ramos-Levi, A. et al. Levels of regulatory T cells CD69+NKG2D+IL-10+ are increased in patients with autoimmune thyroid disorders. Endocrine 51, 478–489 (2016). https://doi.org/10.1007/s12020-015-0662-2

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