Activated and interferon-γ producing thyroid-derived T cells are detected in Graves' disease, thyroid autonomy as well as in non-toxic multinodular goiter

Abstract

The relative numbers of activated and interferon gamma (IFN-gamma)-producing peripheral blood lymphocytes (PBL) and thyroid-derived lymphocytes (TL) were determined using double surface and intracellular labeling techniques in flow cytometry. Cells were analyzed from 10 patients with Graves' disease (GD), eight patients with thyroid autonomy (TA) and five patients with non-toxic multinodular goiter (NTG). A maximum of 1% IFN-gamma+ cells were detected both in unstimulated PBL and TL. Stimulation caused a two- to threefold higher number of IFN-gamma+ cells in TL (GD, 48 +/- 12%; TA, 48 +/- 11%; NTG, 50 +/- 15%) as compared to PBL (GD, 15 +/- 7%; TA, 16 +/- 8%, NTG, 18 +/- 10%) of the same patients. Nearly all IFN-gamma+ TL in GD were CD3+ T cells, whereas 10-20% of IFN-gamma+ TL in TA and NTG were NK cells. In PBL 80% and in TL almost 100% of IFN-gamma+ cells were antigen-primed CD45RO+ cells. Only 25-35% of IFN-gamma+ thyroid-derived T cells expressed the CD4 antigen. About 42 +/- 10% thyroid-derived T cells in GD, 33 +/- 11% in TA and 34 +/- 13% in NTG expressed the HLA-DR molecule but not the interleukin 2 (CD25) or the transferrin receptor (CD71). Forty per cent of these HLA-DR+ T cells showed an intracellular staining for IFN-gamma and half of them co-expressed the activation antigen CD69. Immunofluorescence double labeling on thyroid cryostat sections demonstrated that HLA-DR+ T cells were also present in situ. The presence of activation antigens on thyroid-derived T cells not only in patients with GD but also in TA and NTG suggests failsafe mechanisms such as anergy, suppression or cytokine regulation in so-called non-immunogenic goiter.

Expression of tumour necrosis factor-alpha (TNF-α) mRNA and protein in pathological thyroid tissue and carcinoma cell lines

“…The results obtained in autoimmune thyroid diseases overlapped with those of NTG and TA (perinodular tissue). However, it has been suggested by some authors that immune mechanisms may also be involved in the pathogenesis of toxic and non-toxic goitre [18,[23][24][25][26][27].…”

“…The method for intracellular staining of unstimulated and stimulated thyroid-derived lymphocytes has been described in detail [18]. Cells were incubated for simultaneous surface staining with 10 l FITC-labelled anti-TNF-antibody (Hölzel Diagnostika, Köln, Germany) and with 10 l of a direct labelled MoAb (Becton Dickinson and Dako).…”

Microvascular Endothelial Cells Differ in Their Basal and Tumour Necrosis Factor-α-Regulated Expression of Adhesion Molecules and Cytokines

“…For flow cytometry, 3 × 10 5 MVEC were incubated with the primary antibody at the desired concentration for 20 min at 4°C [5, 20]. The cells were washed three times between each incubation step with PBS/0.1% FCS.…”

Graves’ disease and Hashimoto’s thyroiditis in monozygotic twins: case study as well as transcriptomic and immunohistological analysis of thyroid tissues

“…However, maintenance of the lymphocytic infiltrate in AITD tissues is not static. The presence of activated T-cells in the thyroid (19,20) and increasing variability of T-cell clones and auto-antibody affinity during the course of AITD (1,21,22), even after treatment, reflects the longstanding active immunological processes in the thyroid. Thus, comparison between HT and GD thyroid transcript patterns within identical genetic background and management may give an insight into different immune and remodeling processes.…”