PHENOTHIAZINE INDUCES DE-NOVO MHC CLASS-II ANTIGEN EXPRESSION ON THYROID EPITHELIAL-CELLS - A NEW MECHANISM FOR DRUG-INDUCED AUTOIMMUNITY

Autoimmune responses are initiated by MHC class II-restricted T cell r esponses directed against tissue-specific autoantigens. Furthermore, H LA-DR expression in thyroid epithelial cells is a prominent feature of autoimmune thyroid disease. In the present work, we were particularly interested in a phenothiazine, a neuroleptic and anti-depressant drug of pharmacologic importance named alimemazine. Our interest in this c ompound stems from previous findings of immune effects of th is and ot her phenothiazines. We demonstrate that MHC class II Ags can be experi mentally induced on thyroid cells by pharmacologic concentrations of a limemazine, a drug commonly used in psychiatry. In contrast, MHC class II Ags were not induced on the lymphoid cell lines Raji and Jurkat. E xpression of MHC class II Ag on the surface of the cloned human thyroi d cell hybridoma, GEJ, was demonstrated by flow cytometry. Moreover, b y using Northern blot and Southern blot analyses, this finding was con firmed at the molecular level in GEJ and in murine thyroid epithelial cell cultures, respectively. The functional role of phenothiazine-, de novo-induced MHC class Il Ags on thyroid cells was assessed by both s yngeneic murine thyroglobulin-specific and allogeneic proliferative T cell responses. These results suggest that antidepressant drugs of the phenothiazine type could play a role in the induction and the perpetu ation of thyroid autoimmune disorders, through induction of class II r estriction elements on normally class II-negative thyroid epithelial c ells.