SIMULTANEOUS EXPRESSION OF THYROID PEROXIDASE AND HUMAN-LEUKOCYTE ANTIGEN-DR BY HUMAN THYROID-CELLS - MODULATION BY THYROTROPIN, THYROID-STIMULATING ANTIBODY, AND INTERFERON-GAMMA

Major histocompatibility class II molecules human leukocyte antigen-DR (HLA-DR) are abnormally expressed by human thyroid cells (HTC) in aut oimmune thyroid glands. The simultaneous expression of HLA-DR and orga n-specific autoantigens such as thyroid peroxidase (TPO) by HTC might enable these cells to function as antigen-presenting cells, thus perpe tuating the autoimmune process. The aim of the present study was to cl arify the interplay of endocrine (TSH) and immune [TSab or interferon- gamma (IFN gamma)] factors on the expression of HLA-DR and TPO in HTC. Thyrocytes were cultured with super natants of T-cells cloned from th e infiltrate of Hashimoto's glands, human recombinant IFN gamma, TSab, or TSH. These factors were added either alone or in different combina tions and sequences. HLA-DR and TPO were identified in HTC by a double indirect immunofluorescence technique, using a monoclonal anti-HLA-DR antibody and human serum containing anti-TPO antibody, respectively. IFN gamma, either recombinant or produced by T-cell clones, induced HL A-DR appearance in thyrocytes, whereas TSH or TSab stimulated TPO expr ession. The appearance of HLA-DR induced by IFN gamma was accompanied by a progressive reduction of TPO despite stimulation by TSH or TSab. This decline reached a nadir after 9-10 days in different primary cult ures. During this period, a percentage of cells ranging from 10-40% si multaneously expressed HLA-DR and TPO on their surface and in the cyto plasm. The inhibition of TPO expression and the appearance of HLA-DR i nduced by IFN gamma were rapidly reverted when TSH or TSab was substit uted for interleukin in the culture medium and vice versa. We conclude that 1) the expression of TPO or HLA-DR in thyroid cells is a dynamic phenomenon that is differently influenced by TSH, TSab, and IFN gamma . It is the interplay of these factors in different follicles and duri ng different periods of time that determines the expression of TPO alo ne, HLA-DR alone, or both molecules together in the same thyroid cell; 2) during exposure to TSH (or TSab) and IFN gamma, TPO and HLA-DR can be expressed simultaneously by thyroid cells for up to 7 days; and 3) the modulation of HLA-DR and TPO by supernatants of T-cells cloned fr om Hashimoto's glands is reproduced by IFN gamma alone.