Nontoxic Nodular Goiter and Papillary Thyroid Carcinoma Are Not Associated With Peripheral Blood Lymphocyte Sensitization to Thyroid Cells*

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Abstract
We tested the claim that uni- and multinodular goiter (UNG and MNG) and papillary carcinoma (PC) of the thyroid are autoimmune thyroid diseases (AITD) similar to Graves' disease (GD) and Hashimoto's thyroiditis (HT). The expression of HLA-DR on cultured thyroid epithelial cells (thyrocytes) from UNG, MNG, and PC after coculture with autologous peripheral blood mononuclear cells (PBMC) was compared with that on GD and HT cells. The thyrocytes also were cultured with interferon-γ (IFNγ) alone. A cytotoxicity assay involving 51Cr-labeled thyrocytes, anti-HLA-DR, and complement was used to determine HLA-DR expression. Stimulation of thyrocytes with 200 U/mL IFNγ induced HLA-DR (expressed as a cytotoxicity index) equally well on all thyrocytes [AITD (n = 6): IFN7, 23.8 ± 7.7 (±SD); unstimulated, 3.6 ± 2.0; UNG (n = 6), MNG (n = 9), and PC (n = 5): IFN7, 22.5 ± 4.7;unstimulated, 4.0 ± 3.0]. When cocultured with autologous PBMC, the values were: AITD, 24.9 ± 10.1; UNG, MNG, and PC, 3.8 ± 3.7 (P < 0.001). The supernatants from the AITD cocultures had higher IFNγ concentrations (by RIA) than those from the other cocultures. We conclude that in UNG, MNG, and PC, the peripheral blood helper T-lymphocytes are not sensitized to thyrocyte membrane antigen(s); consequently, little if any IFNγ is produced in cocultures, and hence, there is no increase in thyrocyte HLA-DR expression, unlike the situation in AITD (GD and HT). Thus, UNG, MNG, and PC are not primarily autoimmune in nature, as defined by a lack of sensitization of the PBMC of such patients to thyroid antigen(s).

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