Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self (original) (raw)

• Nossal, G. J. Negative selection of lymphocytes. Cell 76, 229–239 (1994).
  Article CAS Google Scholar
• Goodnow, C. C., Adelstein, S. & Basten, A. The need for central and peripheral tolerance in the B cell repertoire. Science 248, 1373–1379 (1990).
  Article CAS Google Scholar
• Von Boehmer, H. & Kisielow, P. Self-nonself discrimination by T cells. Science 248, 1369–1373 (1990).
  Article CAS Google Scholar
• Stockinger, B. T lymphocyte tolerance: from thymic deletion to peripheral control mechanisms. Adv. Immunol. 71, 229–265 (1999).
  Article CAS Google Scholar
• Miller, J. F. A. P. & Heath, W. H. Self-ignorance in the peripheral T-cell pool. Immunol. Rev. 133, 131–150 (1993).
  Article CAS Google Scholar
• Hanahan, D. Peripheral-antigen-expressing cells in the thymic medulla: factors in self-tolerance and autoimmunity. Curr. Opin. Immunol. 10, 656–662 (1998).
  Article CAS Google Scholar
• Klein, L. & Kyewski, B. Promiscuous expression of “tissue-antigens” in the thymus: A key to T-cell tolerance and autoimmunity? J. Mol. Med. 78, 483–494 (2000).
  Article CAS Google Scholar
• Pugliese, A. et al. The Insulin gene is transcribed in the human thymus and transcription levels correlate with allelic variation at the INS VNTR-_IDDM_2 susceptibility locus for type 1 diabetes. Nature Genet. 15, 293–297 (1997).
  Article CAS Google Scholar
• Vafiadis, P. et al. Insulin expression in human thymus is modulated by INS VNTR alleles at the _IDDM_2 locus. Nature Genet. 15, 289–292 (1997).
  Article CAS Google Scholar
• Egwuagu, C. E., Charukamnoetkanok, P. & Gery, I. Thymic expression of autoantigens correlates with resistance to autoimmune disease. J. Immunol. 159, 3109–3112 (1997).
  CAS PubMed Google Scholar
• Liu, H., MacKenzie-Graham, J., Kim, S. & Voskuhl, R. R. Mice resistant to experimental autoimmune encephalomyelitis have increased thymic expression of myelin basic protein and increased MBP specific T cell tolerance. J. Neuroimmunol. 115, 118–126 (2001).
  Article CAS Google Scholar
• Klein, L., Klugmann, M., Nave, K.-A., Tuohy, V. K. & Kyewski, B. Shaping of the autoreactive T-cell repertoire by a splice variant of self protein expressed in thymic epithelial cells. Nature Med. 6, 56–61 (2000).
  Article CAS Google Scholar
• Anderson, A. C. et al. High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naïve mice: mechanisms of selection of the self-reactive repertoire. J. Exp. Med. 191, 761–770 (2000).
  Article CAS Google Scholar
• Tuohy V. K. et al. The epitope spreading cascade during progression of experimental autoimmune encephalomyelitis and multiple sclerosis. Immunol. Rev. 164, 93–100 (1998).
  Article CAS Google Scholar
• Smith, K. M., Olson, D. C., Hirose, R. & Hanahan, D. Pancreatic gene expression in rare cells of thymic medulla: evidence for functional contribution to T cell tolerance. Int. Immunol. 9, 1355–1365 (1997).
  Article CAS Google Scholar
• Throsby M. et al. Pancreatic hormone expression in the murine thymus: localization in dendritic cells and macrophages. Endocrinology 139, 2399–2406 (1998).
  Article CAS Google Scholar
• Pugliese, A. et al. Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs. J. Clin. Invest. 107, 555–564 (2001).
  Article CAS Google Scholar
• Heath, W. R. et al. Autoimmune diabetes as a consequence of locally produced interleukin-2. Nature 359, 547–549 (1992).
  Article CAS Google Scholar
• Antonia, S. J., Geiger, T., Miller, J. & Flavell, R. A. Mechanisms of immune tolerance induction through the thymic expression of a peripheral tissue-specific protein. Int. Immunol. 7, 715–725 (1994).
  Article Google Scholar
• Klein, L., Klein, T., Ruether, U. & Kyewski, B. CD4 T cell tolerance to human C-reactive protein, an inducible serum protein, is mediated by medullary thymic epithelium. J. Exp. Med. 188, 1–16 (1998).
  Article Google Scholar
• Klein, L., Roettinger, B. & Kyewski, B. Sampling of complementing self-antigen pools by thymic stromal cells maximizes the scope of central T cell tolerance. Eur. J. Immunol. 31, 2476–2486 (2001).
  Article CAS Google Scholar
• Nehls, M. et al. Two genetically separable steps in the differentiation of thymic epithelium. Science 272, 886–889 (1996).
  Article CAS Google Scholar
• Nakagawa, T. et al. Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus. Science 280, 450–453 (1998).
  Article CAS Google Scholar
• Heino, M. et al. Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla. Biochem. Biophys. Res. Commun. 257, 821–825 (2000).
  Article Google Scholar
• Heino, M. et al. RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur. J. Immunol. 30, 1884–1893 (2000).
  Article CAS Google Scholar
• Jolicoeur, C., Hanahan, D. & Smith, K. M. T-cell tolerance toward a transgenic β-cell antigen and transcription of endogenous pancreatic genes in thymus. Proc. Natl Acad. Sci. USA 91, 6707–6711 (1994).
  Article CAS Google Scholar
• Sospedra, M. et al. Transcription of a broad range of self-antigens in human thymus suggests a role for central mechanisms in tolerance toward peripheral antigens. J. Immunol. 161, 5918–5929 (1998).
  CAS PubMed Google Scholar
• Heath, V. L. et al. Intrathymic expression of genes involved in organ specific autoimmune disease. J. Autoimm. 11, 309–318 (1998).
  Article CAS Google Scholar
• Diez, J. et al. Differential splicing of the IA-2 mRNA in pancreas and lymphoid organs as a permissive genetic mechanism for autoimmunity against IA-2 type 1 diabetes. Diabetes 50, 895–900 (2001).
  Article CAS Google Scholar
• Degermann, S., Surh, C. D., Glimcher, L. H., Sprent, J. & Lo, D. B7 expression on thymic medullary epithelium correlates with epithelium-mediated deletion of Vβ5+ thymocytes. J. Immunol. 152, 3254–3263 (1994).
  CAS PubMed Google Scholar
• Naspetti, M. et al. Thymocytes and RelB-dependent medullary epithelial cells provide growth-promoting and organization signals, respectively, to thymic medullary stromal cells. Eur. J. Immunol. 27, 1392–1397 (1997).
  Article CAS Google Scholar
• Jamieson, B. S. et al. Generation of functional thymocytes in the human adult. Immunity 10, 569–575 (1999).
  Article CAS Google Scholar
• Naquet, P., Naspetti, M. & Boyd, R. Development, organization and function of the thymic medulla in normal, immunodeficient or autoinmmune mice. Semin. Immunol. 11, 47–55 (1999).
  Article CAS Google Scholar
• Van Ewijk, W., Holländer, G., Terhorst, C. & Wang, B. Stepwise development of thymic microenvironments in vivo is regulated by thymocyte subsets. Development 127, 1583–1591 (2000).
  CAS PubMed Google Scholar
• Shinkai, Y. et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68, 855–867 (1992).
  Article CAS Google Scholar
• Chan, S. et al. Another view of the selective model of thymocyte selection. Cell 73, 225–236 (1993).
  Article CAS Google Scholar
• Hecht, N. B. The making of a spermatozoon: a molecular perspective. Dev. Genet. 16, 95–103 (1995).
  Article CAS Google Scholar
• Pepys, M. B., Baltz, M., Gomer, K., Davies, A. J. S. & Doenhoff, M. Serum amyloid P-component is an acute-phase reactant in mouse. Nature 278, 259–261 (1979).
  Article CAS Google Scholar
• Pepys, M. B. & Baltz, M. L. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Adv. Immunol. 34, 141–212 (1983).
  Article CAS Google Scholar
• Botto, M. et al. Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene. Nature Med. 3, 855–859 (1997).
  Article CAS Google Scholar
• Chelly, J., Concordet, J. P., Kaplan, J. C. & Kahn. A. Illegitimate transcription: transcription of any gene in any cell type. Proc. Natl Acad. Sci. USA 86, 2617–2621 (1989).
  Article CAS Google Scholar
• Sarakar, G. & Sommer, S. S. Access to a messenger RNA sequence or its protein product is not limited by tissue or species specificity. Science 244, 331–334 (1989).
  Article Google Scholar
• Gygi, S., Rochon, Y., Franza, B. R. & Aebersold, R. Correlation between protein and mRNA abundance in yeast. Mol. Cell. Biol. 19, 1720–1730 (1999).
  Article CAS Google Scholar
• Kojima, K., Reindl, M., Lassmann, H., Wekerle, H. & Linington. C. The thymus and self-tolerance: co-existence of encephalitogenic S100 β-specific T cells and their nominal autoantigen in the normal adult rat thymus. Int. Immunol. 9, 897–904 (1997).
  Article CAS Google Scholar
• Targoni, O. S. & Lehmann, P. V. Endogenous myelin basic protein inactivates the high avidity T cell repertoire. J. Exp. Med. 187, 2055–2063 (1998)
  Article CAS Google Scholar
• Harrington, C. J. et al. Differential tolerance is induced in T cells recognizing distinct epitopes of myelin basic protein. Immunity 8, 571–580 (1998).
  Article CAS Google Scholar
• Volkmann, A. & Stockinger, G. Antigen-presenting cells in the thymus that can negatively select MHC class II-restricted T cells recognizing a circulating self-antigen. J. Immunol. 158, 693–706 (1997).
  CAS PubMed Google Scholar
• Links, R., Gottesman, M. & Pernis, B. Are tissues a patch quilt of ectopic gene expression? Science 246, 261 (1989).
  Google Scholar
• Farr, A. G. & Rudensky, A. 1998. Medullary thymic epithelium: a mosaic of epithelial “self”? J. Exp. Med. 188, 1–4 (1998).
  Article CAS Google Scholar
• Boon T, Coulie, G. & van den Eynde, B. Tumor antigens recognized by T cells. Immunol. Today 18, 267–268 (1997).
  Article CAS Google Scholar
• Morgan, D. J. et al. Activation of low avidity CTL specific for self epitope results in tumor rejection but not autoimmunity. J. Immunol. 160, 643–651 (1998).
  CAS PubMed Google Scholar
• De Visser, K. E. et al. Tracing and characterization of the low-avidity self-specific T cell repertoire. Eur. J. Immunol. 30, 1458–1468 (2000).
  Article CAS Google Scholar
• Seddon, B. & Mason, D. The third function of the thymus. Immunol. Today 21, 95–99 (2000).
  Article CAS Google Scholar
• Sakaguchi, S. Regulatory T cells: key controllers of immunologic self tolerance. Cell 101, 455–458 (2000).
  Article CAS Google Scholar
• Jordan, M. S. et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nature Immunol. 2, 301–306 (2001).
  Article CAS Google Scholar
• Le Douarin, N. et al. Evidence for a thymus-dependent form of tolerance that is not based on elimination or anergy of reactive T cells. Immunol. Rev. 149, 35–53 (1996).
  Article CAS Google Scholar
• Klein, L. & Kyewski, B. Self-antigen presentation by thymic stromal cells: a subtle division of labor. Curr. Opin. Immunol. 12, 179–186 (2000).
  Article CAS Google Scholar
• Peterson, P. et al. APECED: a monogenic autoimmune disease providing new clues to self-tolerance. Immunol. Today 19, 384–386 (1998).
  Article CAS Google Scholar
• Pepys, M. B. Isolation of serum amyloid P component (protein SAP) in the mouse. Immunology 37, 637–641 (1979).
  CAS PubMed PubMed Central Google Scholar
• Jung, M., Sommer, I., Schachner, M. & Nave, K.-A. Monoclonal antibody 010 defines a conformationally sensitive cell-surface epitope of proteolipid protein (PLP): evidence that PLP misfolding underlies dysmyelination in mutant mice. J. Neurosci. 16, 7920–7929 (1996).
  Article CAS Google Scholar
• Amar-Costesec, A., Godelaine, D., Van den Eynde, B. & Beaufy, H. Identification and characterization of the tumor-specific P1A gene product. Biol. Cell 81, 195–203 (1994).
  Article CAS Google Scholar
• den Haan, J. M., Lehar, S. M. & Bevan, M. J. CD8+ but not CD8- dendritic cells cross-prime cytotoxic T cells in vivo. J. Exp. Med. 192, 1685–1696 (2000).
  Article CAS Google Scholar
• Born, W. & Wekerle, H. Selective, immunologically nonspecific adherence of lymphoid and myeloid cells to Leydig cells. Eur. J. Cell Biol. 25, 76–81 (1981).
  CAS PubMed Google Scholar