DO HEAT-SHOCK PROTEINS PLAY A ROLE IN GRAVES-DISEASE - HEAT-SHOCK PROTEIN-SPECIFIC T-CELLS FROM GRAVES-DISEASE THYROIDS DO NOT RECOGNIZE THYROID EPITHELIAL-CELLS

Thyroid-derived T-cells from patients with Graves' disease were analyz ed for their reactivity to recombinant heat shock proteins (hsp) and a utologous thyroid epithelial cells (TEC). Five of six uncloned T-cell lines responded to stimulation with recombinant mycobacterial 71-kilod alton (kDa) hsp and cross-reacted with the corresponding amoebial and human proteins. Only one line reacted with recombinant 65-kDa hsp. Thy roid-derived T-cell lines also showed a proliferative response to TEC, which could be increased in four of the lines, when hsp expression wa s induced in thyroid cells by heat stress before the initiation of coc ulture. Clonal specificity analysis of thyroid-derived T-cell clones, however, demonstrated that distinct T-cells were responsible for the r ecognition of recombinant hsp and TEC. None of the clones responsive t o recombinant hsp recognized TEC, whereas TEC-responsive clones did no t react with recombinant hsp. Interestingly, the response of the major ity of TEC-reactive clones could be dramatically increased when heat-s hocked TEC were used as stimulator cells. These results suggest that T -cells specific for hsp of the 70- or 60-kDa families do not recognize TEC in the autoimmune thyroid gland. Heat shock-inducible proteins ma y, however, still play a role in the autoimmune process by facilitatin g the presentation of thyroid-specific autoantigen(s) to autoreactive T-cells.