Thyroid autoantigens andhumanT cell responses

SUMMARY Weinvestigated theability ofT cells frompatients withHashimoto's thyroiditis andwithGraves' disease as wellas control donorstoproliferate inresponsetothyroid peroxidase (TPO)and thyroglobulin using (i) lymphoid cells fromdifferent lymphoid organs;(ii) unfractionated orCD8depleted lymphoid suspensions or T cells +autologous lowdensity cells (LDC); (iii) 200-pl well cultures and20-pl hanging-drop microcultures; and(iv) intact TPO andthyroglobulin, denatured thyroglobulin and12synthetic peptides predicted on thebasis oftheaminoacidsequenceofTPO to beTcell epitopes. In200-pl wellcultures, proliferative responses(assessed intermsof3H-thymidine uptake) tointact TPO orthyroglobulin, digested thyroglobulin orsynthetic TPO peptides werenot significantly different inunfractionated orCD8-depleted lymphoid suspensions fromblood, thyroid or lymphnodesofTPO/thyroglobulin autoantibody-positive patients, autoantibody-negative patients orcontrol donors. Incontrast, blood Tcells fromsome high titre patients withHashimoto's thyroiditis (but notfromhealthy individuals) proliferated inresponsetointact thyroglobulin orTPO presented byautologous LDC inhanging-drop microcultures. Heatdenatured thyroglobulin (with whichthyroglobulin autoantibodies do notinteract) didnotstimulate proliferation andthis observation, together withtheability ofTcells fromsome patients torespond tointact thyroglobulin intheabsence ofLDC,indicated thatthyroglobulin-specific B cells may beinvolved inantigen presentation. Aswe were unable todemonstrate proliferation bybloodT cells+ LDC fromall thyroglobulin antibody-positive patients withHashimoto's thyroiditis, our studies suggest thatthe presenceofsufficient precursorTcells, aswell asthenumberandtypeofantigen-presenting cells, are critical forTcell proliferative responsestohumanTPOandthyroglobulin.