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.

Quantitative and functional analysis of CD69+ T regulatory lymphocytes in patients with periodontal disease

“…Thus, the aim of this study was to analyze the levels and function of CD69 + Treg cells in patients with PD. In this regard, we and others have recently described that although the frequency of these cells is low in peripheral blood, they seem to exert a relevant immune regulatory function, inhibiting the activation and proliferation of effector lymphocytes .…”

“…Since we have previously observed that a subset of CD69 + Treg cells expresses the activation marker NKG2D , we decided to include this receptor in our flow cytometry analysis. As shown in Fig.…”

“…Thus, the possible contribution of Treg cell subsets different from those described by Sakaguchi (7,8) to the pathogenesis of PD has not been explored. In this regard, we have recently detected that patients with autoimmune thyroiditis show increased levels of CD69 + NKG2D + IL-10 + Treg lymphocytes in their peripheral blood and thyroid tissue, with a defective immunosuppressive function (23). Furthermore, we have observed that patients with generalized autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis, also show abnormalities in the number and function of CD69 + Treg lymphocytes (14).…”

Impaired immune regulation after radioiodine therapy for Graves’ disease and the protective effect of Methimazole

“…In murine models, lack of Treg aggravates the development of GD [8,35]. The thyroid of patients with GD is infiltrated with high proportion of Treg compared to autologous peripheral blood [36]. However, the role of Treg in GD pathogenesis remains to be elucidated in terms of Treg phenotype and function during the course of the disease and in terms of the plasticity of this subgroup of lymphocytes [37].…”

Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment

“…Since activated T cells stimulate B cells to proliferate and secrete antibodies (IgG), B cell tolerance mechanisms are considered as a secondary mechanism [13] . Tregs suppress immune responses against self or non-self Ags, producing immunosuppressive cytokines [interleukin-10 (IL-10), and transforming growth factor β (TGF-β)] and Tregs are dysfunctional in AITD patients [14,15] .…”