Intrathymic Expression of Genes Involved in Organ Specific Autoimmune Disease

• Published in: Journal of autoimmunity Vol. 11; no. 4; pp. 309 - 318
• Main Authors: Heath, Victoria L, Moore, Nel C, Parnell, Sonia M, Mason, Don W
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 01-08-1998; Elsevier
• Subjects: Animals; Autoantigens - genetics; Autoantigens - immunology; Autoimmune Diseases - genetics; Autoimmune Diseases - metabolism; Biological and medical sciences; central tolerance; DNA, Complementary - genetics; DNA, Complementary - metabolism; General aspects; Immunopathology; insulin; Insulin - biosynthesis; Insulin - genetics; Male; Medical sciences; Mice; myelin basic protein; Myelin Basic Protein - biosynthesis; Myelin Basic Protein - genetics; Organ Culture Techniques; Organ Specificity; Rats; Rats, Inbred Strains; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; thymus; Thymus Gland - immunology; Thymus Gland - metabolism; thyroglobulin; Thyroglobulin - biosynthesis; Thyroglobulin - genetics; thymus; central tolerance; myelin basic protein; insulin; thyroglobulin; Endocrinopathy; Human; Thyroiditis; Immunopathology; Nervous system diseases; Multiple sclerosis; Thymus gland; Thyroid diseases; Exploration; Autoimmune disease; Gene expression; Inflammatory disease; Autoantigen; Messenger RNA; Central nervous system disease; Insulin dependent diabetes; Molecular biology
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.1998.0210

Insulin, thyroglobulin and myelin basic protein (MBP) are implicated as autoantigens in the autoimmune diseases, insulin-dependent diabetes mellitus (IDDM), autoimmune thyroid-disease and multiple sclerosis. Self tolerance to these antigens, until recently only thought to be present extrathymically, is generally considered to be maintained by ‘peripheral’ mechanisms, such as clonal anergy or clonal ignorance. The techniques 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 thymus, various mouse thymic cell-types isolated from fetal thymic-organ cultures and from neonatal-mouse thymocyte subsets. mRNA for insulin, thyroglobulin and MBP were detected in unfractionated adult rat and embryonic 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 cells and class II+dendritic cells and in certain thymocyte subsets. The presence of insulin, thyroglobubin and MBP mRNA in the thymus has important implications for the development of the T-cell repertoire, particularly for the mechanisms of tolerance that prevent autoreactivity to these antigens in healthy individuals.