SPONTANEOUS AUTOIMMUNE-DISEASE IN (NZB X NZW)F-1 MICE IS AMELIORATED BY TREATMENT WITH METHIMAZOLE

(NZB X NZW)F-1 mice spontaneously develop with age an autoimmune disea se that resembles the human disease, systemic lupus erythematosus (SLE ). The present study demonstrates that methimazole (MMI), an agent use d in the treatment of autoimmune thyroid disease, is effective in miti gating the development of this SLE-like autoimmune disease in (NZB x N ZW)F-1 mice. MMI significantly reduces the incidence and severity of p roteinuria and deposition of immune complexes in the kidney. Previous studies have demonstrated that development of an experimentally induce d SLE, which was prevented by MMI treatment, depended on the expressio n of MHC class I molecules. We now report that class I levels on both T cells and B cells from old (NZB X NZW)F-1 MHC class I are markedly e levated relative to those from young F-1 mice. Furthermore, treatment of(NZB X NZW)F-1 mice with MMI reduced MHC class I expression on their PBL concomitant with amelioration of disease, raising the possibility that class I molecules may play a role in the generation of spontaneo us autoimmune disease in these mice.