ACTIVATED AND INTERFERON-GAMMA PRODUCING THYROID-DERIVED T-CELLS ARE DETECTED IN GRAVES-DISEASE, THYROID AUTONOMY AS WELL AS IN NONTOXIC MULTINODULAR GOITER

The relative numbers of activated and interferon gamma (IFN-gamma)-pro ducing peripheral blood lymphocytes (PBL) and thyroid-derived lymphocy tes (TL) were determined using double surface and intracellular labeli ng techniques in flow cytometry. Cells were analyzed from 10 patients with Graves' disease (GD), eight patients with thyroid autonomy (TA) a nd five patients with non-toxic multinodular goiter (NTG). A maximum o f 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 compa red 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, where as 10-20% of IFN-gamma(+) TL in TA and NTG were NI( 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 express ed 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), Fort y per cent of these HLA-DR(+) T cells showed an intracellular staining for IFN-gamma and half of them co-expressed the activation antigen CD 69. Immunofluorescence double labeling on thyroid cryostat sections de monstrated that HLA-DR(+) T cells were also present in situ, The prese nce of activation antigens on thyroid-derived T cells not only in pati ents with GD but also in TA and NTG suggests failsafe mechanisms such as anergy, suppression or cytokine regulation in so-called non-immunog enic goiter.