Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self.
Expression of peripheral antigens in the thymus has been implicated in T cell tolerance and autoimmunity. Here we identified medullary thymic epithelial cells as being a unique cell type that expresses a diverse range of tissue-specific antigens. We found that this promiscuous gene expression was a cell-autonomous property of medullary epithelial cells and was maintained during the entire period of thymic T cell output. It may facilitate tolerance induction to self-antigens that would otherwise be temporally or spatially secluded from the immune system. However, the array of promiscuously expressed self-antigens appeared random rather than selected and was not confined to secluded self-antigens.
Derbinski
J
J
Tumor Immunology Program, Division of Cellular Immunology, German Cancer Research Center, INF 280, D-69120, Germany.
Schulte
A
A
Kyewski
B
B
Klein
L
L
D000818:Animals; D001324:Autoantigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009928:Organ Specificity; D011828:Radiation Chimera; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017634:Self Tolerance / Q000235:genetics*; D000683:Serum Amyloid P-Component / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000378:metabolism* / Q000637:transplantation; D014157:Transcription Factors / Q000378:metabolism
D001324:Autoantigens; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D000683:Serum Amyloid P-Component; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2