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 autoimmune thyroid glands. The simultaneous expression of HLA-DR and organ-specific autoantigens such as thyroid peroxidase (TPO) by HTC might enable these cells to function as antigen-presenting cells, thus perpetuating the autoimmune process. The aim of the present study was to clarify 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 supernatants of T-cells cloned from the infiltrate of Hashimoto's glands, human recombinant IFN gamma, TSab, or TSH. These factors were added either alone or in different combinations 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 HLA-DR appearance in thyrocytes, whereas TSH or TSab stimulated TPO expression. 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 cultures. During this period, a percentage of cells ranging from 10-40% simultaneously expressed HLA-DR and TPO on their surface and in the cytoplasm. The inhibition of TPO expression and the appearance of HLA-DR induced by IFN gamma were rapidly reverted when TSH or TSab was substituted 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 during different periods of time that determines the expression of TPO alone, 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 from Hashimoto's glands is reproduced by IFN gamma alone.
Chiovato
L
L
Istituto di Endocrinologia, University of Pisa, Italy.
Lapi
P
P
Mariotti
S
S
Del Prete
G
G
De Carli
M
M
Pinchera
A
A
D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000494:pharmacology*; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006684:HLA-DR Antigens / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating; D007371:Interferon-gamma / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000032:analysis / Q000378:metabolism*; D011994:Recombinant Proteins; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013967:Thyroiditis, Autoimmune / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D006684:HLA-DR Antigens; D018828:Immunoglobulins, Thyroid-Stimulating; D011994:Recombinant Proteins; D007371:Interferon-gamma; D013972:Thyrotropin; D007453:Iodide Peroxidase