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

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.