Thein VitroRegulation of Human Thyrocyte HLA-DR Antigen Expression*

Abstract

The ability of endocrine organs to express human immune response-associated antigens (Ia), such as HLA-DR, 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 gamma-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 gamma-interferon. The lectin phytohemagglutinin also induced HLA-DR 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 gamma-interferon and phytohemagglutinin. In contrast, neither recombinant alpha-interferon nor interleukin-2 induced HLA-DR antigens. Irradiation reduced the response of thyroid cells to gamma-interferon, but two of the known inhibitors of macrophage Ia expression, prostaglandin E2 and (Bu)2cAMP, did not affect gamma-interferon-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 Ia antigens and, thus, of activating T cells to initiate autoimmune thyroiditis; and 2) once activated, for example by a virus, T cells could release gamma-interferon and induce thyroid cell HLA-DR and -DQ antigen expression; these Ia-positive thyroid cells could then have a role in maintaining or enhancing the autoimmune response.

Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes

“…The presence of γ-IFN has been demonstrated at the site of inflammation (30). In vitro, γ-IFN has been shown to induce de novo class II antigen expression on a variety of human cell types, including vascular endothelial cells and fibroblasts (31,32), AEC (33), glomerular mesangial cells (34) and thyrocytes (35). The class II antigens induced on endothelial cells are functional and can be recognized by cytotoxic T cells (31).…”

Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes

“…The presence of 'Y-IFN has been demonstrated at the site of inflammation (30). In vitro, 'Y-IFN has been shown to induce de novo class II antigen expression on a variety of human cell types, including vascular endothelial cells and fibroblasts (31,32), AEC (33), glomerular mesangial cells (34) and thyrocytes (35). The class II antigens induced on endothelial cells are functional and can be recognized by cytotoxic T cells (31).…”

Modulation of class-II antigen expression in human thyroid epithelial cell cultures

“…In this study we were interested in which potential in vivo regulators of thyroid cell functions could modulate HLA-D expression. We investigated the possibility that there might exist a mechanism to induce HLA-D expression different than the well documented pathway via IFN-y (Todd et al 1985;Davies et al 1985;Weetman et al 1985). Namely, the chronic stimulation of the TSH-receptor and/or the administration of iodine, methimazole, perchlorate, interferon-y, TSH-receptor antibodies in TECs grown in culture medium with or without serum supplementation was studied.…”