Thein VitroRegulation of Human Thyrocyte HLA-DR Antigen Expression*

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Abstract
The ability of endocrine organs to express human immune response-associated antigens (la), such as HLADR, is a subject of intense current interest. In this study, the effects of various potential modulators of thyroid follicular cell HLA-DR expression were examined using in vitro cultures. A culture supernatant containing T-cell-derived lymphokines caused DR antigen expression on 13–18% of thyroid cells; more consistent effects were produced by recombinant ³-interferon, which led to 46–100% of the thyroid cells becoming HLA-DR positive after 3 days in culture. This effect was both time and concentration dependent and occurred in thyroid cells derived from patients with Graves' disease (n = 7) and Hashimoto's thyroiditis (n = 2) as well as from three subjects with no autoimmune thyroid disease. Thyroid cells stained with the monoclonal antibodies 4F2 and 5E9, which recognize cell activation antigens, regardless of whether they were treated with ³- interferon. The lectin phytohemagglutinin also induced HLADR antigen expression (21–91% of cells positive). This response was dependent on T cell contamination of thyroid cell suspensions, since the effect was inhibited by cyclosporin A. HLA-DQ antigen expression, identified by the Leu-10 monoclonal antibody, was also induced on thyroid cells by ³-interferon and phytohemagglutinin. In contrast, neither recombinant a-interferon nor interleukin-2 induced HLA-DR antigens. Irradiation reduced the response of thyroid cells to ³-interferon, but two of the known inhibitors of macrophage la expression, prostaglandin E2 and (Bu)2cAMP, did not affect -³interferon-induced thyroid cell HLA-DR expression. We were unable to detect interleukin- 1 production by thyroid cells. These results suggest that 1) under normal circumstances, thyroid cells are 4F2 and 5E9 positive, but are incapable of expressing la antigens and, thus, of activating T cells to initiate autoimmune thyroiditis; and 2) once activated, for example by a virus, T cells could release ³- interferon and induce thyroid cell HLA-DR and -DQ antigen expression; these la-positive thyroid cells could then have a role in maintaining or enhancing the autoimmune response.

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