ABNORMAL T-CELL SELECTION ON NOD THYMIC EPITHELIUM IS SUFFICIENT TO INDUCE AUTOIMMUNE MANIFESTATIONS IN C571BL 6 ATHYMIC NUDE-MICE/

To investigate the role of primary T cell repertoire selection in the immunopathogenesis of autoimmune diseases, pure thymic epithelium (TE) from nonobese diabetic (NOD) embryos was grafted into non autoimmune prone newborn C57BL/6 athymic mice, The results show that NOD TE selec ts host T cell repertoires that establish autoimmunity in otherwise no ndiabetic animals, Thus, such chimeras regularly show CD4 and CDS T ce ll-mediated insulitis and sialitis, in contrast with syngeneic or allo geneic chimeras produced with TE from nonautoimmune strains, This is t he first demonstration that autoimmunity to pancreatic beta cells and salivary glands can be established by the sole alteration of the thymi c environment involved in T cell selection, regardless of the nature a nd presentation of both major histocompatibility complex and tissue-sp ecific antigens on the target a organ, These data indicate that T cell repertoire selection by the NOD thymic epithelium is sufficient to in duce specific autoimmune characteristics in the context of an otherwis e normal host.