IDENTIFICATION OF THYROID-STIMULATING HORMONE RECEPTOR-SPECIFIC T-CELLS IN GRAVES-DISEASE THYROID USING AUTOANTIGEN-TRANSFECTED EPSTEIN-BARR VIRUS-TRANSFORMED B-CELL LINES
Rj. Mullins et al., 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), 1995, pp. 30-37
The importance of thyrotropin receptor (TSHR) agonist antibodies in th
e manifestations of Graves' disease (GD) is recognized. There are, how
ever, no convincing reports of TSHR-specific T cells. We have previous
ly cloned T cells specific for thyroglobulin and thyroid peroxidase (T
PO) 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 transfec
ted with TSHR to seek TSHR-specific T cells in the GD infiltrates, aft
er 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 s
timulation with soluble anti-CD3 and phorbol ester was indistinguishab
le from the other clones from this thyroid. However, they produced rel
atively little IFN gamma (median IL-4/IFN gamma ratio of 0.80) compare
d with the other clones (median IL-4/IFN gamma ratio 0.06). Thus, this
new potent method of antigen presentation, using autoantigen-transfec
ted EBVL, has permitted the first unequivocal identification of TSHR T
cells in GD thyroid, with distinct Th0/ Th2 characteristics, unlike p
reviously cloned TPO-responsive cells which have Th1 characteristics.