title: Identification of thyroid stimulating hormone receptor-specific T cells in Graves' disease thyroid using autoantigen-transfected Epstein-Barr virus-transformed B cell lines.
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.
authors.affiliation: Mathilda and Terence Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Mullins
authors.forename: S B
authors.initials: SB
authors.lastname: Cohen
authors.forename: L M
authors.initials: LM
authors.lastname: Webb
authors.forename: Y
authors.initials: Y
authors.lastname: Chernajovsky
authors.forename: C M
authors.initials: CM
authors.lastname: Dayan
authors.forename: M
authors.initials: M
authors.lastname: Londei
authors.forename: M
authors.initials: M
authors.lastname: Feldmann
mesh_terms: D017951:Antigen Presentation; D001324:Autoantigens / Q000502:physiology*; D001402:B-Lymphocytes; D002460:Cell Line; D002461:Cell Line, Transformed; D016207:Cytokines / Q000378:metabolism; D006111:Graves Disease / Q000276:immunology*; D004854:Herpesvirus 4, Human; D006801:Humans; D011989:Receptors, Thyrotropin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology*; D014162:Transfection
chemical_list: D001324:Autoantigens; D016207:Cytokines; D011989:Receptors, Thyrotropin