Document 0926
 DOCN  M9540926
 TI    T-cell reactivity to recombinant human thyrotropin receptor
       extracellular domain and thyroglobulin in patients with autoimmune and
       nonautoimmune thyroid diseases.
 DT    9504
 AU    Soliman M; Kaplan E; Fisfalen ME; Okamoto Y; DeGroot LJ; Department of
       Medicine, University of Chicago, Illinois 60637.
 SO    J Clin Endocrinol Metab. 1995 Jan;80(1):206-13. Unique Identifier :
       AIDSLINE MED/95130668
 AB    Grave's disease and Hashimoto's thyroiditis are common organ-specific
       disorders characterized by an immune response toward a number of thyroid
       proteins, including TSH receptor (TSHR), thyroid peroxidase, and
       thyroglobulin (Tg). Although considerable progress has been made in
       understanding and mapping the autoantibody response to TSHR, much less
       is known about recognition of TSHR by pathogenic T-cells in human
       disease. To identify such reactions, we analyzed the T-cell
       proliferative responses of peripheral blood lymphocytes (PBMC) to human
       recombinant TSHR extracellular domain (hrecTSHR-ECD amino acids 19-417)
       expressed in Escherichia coli and to Tg. Forty-two patients with
       autoimmune thyroid disease (AITD), 13 patients with non-AITD, and 20
       normal subjects were studied. PBMC from 40% of patients with AITD and
       46% of patients with non-AITD reacted significantly to hrecTSHR-ECD. The
       reactivity to Tg was less than that to TSHR-ECD in both groups. Five
       percent of normal subjects showed a response to hrecTSHR-ECD and none to
       Tg. TSHR-specific T-cell lines were developed in 16 of 26 AITD patients
       and 3 of 10 non-AITD patients. CD8-positive T-cell depletion from PBMC
       of 8 patients with AITD by the indirect panning method did not enhance
       the reactivity to hrecTSHR-ECD, except in 1 patient. We conclude that
       TSHR-specific T-cells are present in the circulation of patients with
       AITD and are presumably involved in the pathogenesis of thyroid
       autoimmunity. The lower, but positive, reactivity to hrecTSHR-ECD found
       in patients with non-AITD was unexpected and may be related to
       lymphocytic infiltrates in the thyroid of 7 of the 11 patients.
 DE    Adult  Autoimmune Diseases/*PATHOLOGY  Cell Division/DRUG EFFECTS  Cell
       Line  CD8-Positive T-Lymphocytes/PHYSIOLOGY  Female  Human  Male  Middle
       Age  Monocytes/DRUG EFFECTS/PATHOLOGY  Peptide Fragments/*PHARMACOLOGY
       Receptors, Thyrotropin/*CHEMISTRY  Reproducibility of Results  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes/*DRUG
       EFFECTS/PATHOLOGY  Thyroglobulin/*PHARMACOLOGY  Thyroid
       Diseases/*PATHOLOGY  JOURNAL ARTICLE

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