INTRATHYMIC EXPRESSION OF GENES INVOLVED IN ORGAN-SPECIFIC AUTOIMMUNE-DISEASE

Insulin, thyroglobulin and myelin basic protein (MBP) are implicated a s autoantigens in the autoimmune diseases, insulin-dependent diabetes mellitus (IDDM), autoimmune thyroid-disease and multiple sclerosis. Se lf tolerance to these antigens, until recently only thought to be pres ent extrathymically, is generally considered to be maintained by 'peri pheral' mechanisms, such as clonal anergy or clonal ignorance. The tec hniques of reverse transcription and polymerase chain reaction (RT-PCR ) were used to investigate the intrathymic expression of these genes. Expression was examined in mRNA isolated from complete adult rat thymu s, various mouse thymic cell-types isolated from fetal thymic-organ cu ltures and from neonatal-mouse thymocyte subsets. mRNA for insulin, th yroglobulin and MBP were detected in unfractionated adult rat and embr yonic mouse thymus. Rat thymus expressed both insulin I and II, while mouse thymus only expressed insulin II. Thyroglobulin and MBP, but not insulin mRNA were detected in mouse MHC class II+ thymic epthelial ce lls and class II+ dendritic cells and in certain thymocyte subsets. Th e presence of insulin, thyroglobubin and MBP mRNA in the thymus has im portant implications for the development of the T-cell repertoire, par ticularly for the mechanisms of tolerance that prevent autoreactivity to these antigens in healthy individuals. (C) 1998 Academic Press.