T-cell reactivity to recombinant human thyrotropin receptor extracellular domain and thyroglobulin in patients with...

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.