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Identification of thyroid stimulating hormone receptor-specific T cells in Graves' disease thyroid using autoantigen-transfected Epstein-Barr virus-transformed B cell lines

Mullins, R. J., Cohen, S. B., Webb, L. M., Chernajovsky, Y., Dayan, Colin Mark, Londei, M. and Feldmann, M. 1995. Identification of thyroid stimulating hormone receptor-specific T cells in Graves' disease thyroid using autoantigen-transfected Epstein-Barr virus-transformed B cell lines. The Journal of Clinical Investigation 96 (1) , pp. 30-37. 10.1172/jci118034

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Abstract

The importance of thyrotropin receptor (TSHR) agonist antibodies in the manifestations of Graves' disease (GD) is recognized. There are, however, no convincing reports of TSHR-specific T cells. We have previously cloned T cells specific for thyroglobulin and thyroid peroxidase (TPO) from GD lymphoid infiltrates and used autologous EBV-transformed B cell lines (EBVL) transfected with an expression vector encoding TPO to efficiently detect TPO-specific T cells. Here we used EBVL transfected with TSHR to seek TSHR-specific T cells in the GD infiltrates, after cloning the in vivo activated T cells without antigen. 3 out of 30 clones responded vigorously and reproducibly to EBVL-TSHR, with a mean stimulation index > 7. Their release of IL-2, IL-4, and IL-10 after stimulation with soluble anti-CD3 and phorbol ester was indistinguishable from the other clones from this thyroid. However, they produced relatively little IFN gamma (median IL-4/IFN gamma ratio of 0.80) compared with the other clones (median IL-4/IFN gamma ratio 0.06). Thus, this new potent method of antigen presentation, using autoantigen-transfected EBVL, has permitted the first unequivocal identification of TSHR T cells in GD thyroid, with distinct Th0/Th2 characteristics, unlike previously cloned TPO-responsive cells which have Th1 characteristics.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RZ Other systems of medicine
Publisher: American Society for Clinical Investigation
ISSN: 0021-9738
Last Modified: 04 Jun 2017 06:41
URI: http://orca.cf.ac.uk/id/eprint/63689

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