Peripheral-antigen-expressing cells in thymic medulla: Factors in self-tolerance acid autoimmunity

Current Opinion in Immunology

Volumn 10, Issue 6, 1998, Pages 656-662

  Hanahan, Douglas ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INSULIN;

ANIMAL CELL; ANTIGEN EXPRESSION; AUTOIMMUNE DISEASE; AUTOIMMUNITY; DISEASE PREDISPOSITION; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNOLOGICAL TOLERANCE; MOUSE; NONHUMAN; REVIEW; THYMUS; THYMUS TRANSPLANTATION; TRANSGENE;

EID: 0032401760     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(98)80085-X     Document Type: Article

References (36)

1. Fowlkes BJ, Ramsdell F. T-cell tolerance. Curr Opin Immunol. 5:1993;873-879.
2. Sprent J, Webbs SR. Intrathymic and extrathymic clonal deletion of T cells. Curr Opin Immunol. 7:1995;196-205.
3. Hammerling GJ, Schonrich G, Ferber I, Arnold B. Peripheral tolerance as a multistep mechanism. Immunol Rev. 133:1993;93-104.
4. Heath V, Mason D, Ramirez F, Seddon B. Homeostatic mechanisms in the control of autoimmunity. of special interest Semin Immunol. 9:1997;375-380 This gives a recent perspective on thymic expression of peripheral-antigen genes and on mechanisms of peripheral tolerance.
5. Van Parijs L, Abbas AK. Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science. 280:1998;243-248.
6. Heath WR, Allison J, Hoffmann MW, Schonrich G, Hammerling G, Arnold B, Miller JFAP. Autoimmune diabetes as a consequence of locally produced interleukin-2. Nature. 359:1992;547-549.
7. von Herrath MG, Dockter J, Oldstone MBA. How virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic model. Immunity. 1:1994;231-242.
8. Jolicoeur C, Hanahan D, Smith KM. T cell tolerance toward a transgenic B cell antigen and transcription of endogenous pancreatic genes in the thymus. Proc Natl Acad Sci USA. 91:1994;6707-6711.
9. Husbands SD, Schönrich G, Arnold B, Chandler PR, Simpson E, Philpott KL, Tomlinson P, O'Reilly L, Cooke A, Mellor AL. Expression of major histocompatibility complex class I antigens at low levels in the thymus induces T cell tolerance via a non-deletional mechanism. Eur J Immunol. 22:1992;2655-2661.
10. Yeomen H, Mellor AL. Tolerance and MHC restriction in transgenic mice expressing a MHC class I gene in erythroid cells. Int Immunol. 4:1992;59-65.
11. Antonia SJ, Geiger T, Miller J, Flavell RA. Mechanisms of immune tolerance induction through the thymic expression of a peripheral tissue-specific protein. Int Immunol. 7:1995;715-725.
12. Palmiter RD, Brinster RL. Germ-line transformation of mice. Annu Rev Genet. 20:1986;465-499.
13. Chelly J, Concordet JP, Kaplan JC, Kahn A. Illegitimate transcription: transcription of any gene in any cell type. Proc Natl Acad Sci USA. 86:1989;2617-2621.
14. Pugliese A, Zeller M, Fernandez A Jr, Zalcberg LJ, Bartlett RJ, Ricordi C, Pietropaolo M, Eisenbarth GS, Bennett ST, Patel DD. The insulin gene is transcribed in the human thymus and transcription levels correlate with the allelic variation at the INS VNTR-IDDM2 susceptibility locus for type1 diabetes. of outstanding interest Nat Genet. 15:1997;293-297 This is one of two papers (with [15]) which report that the human insulin gene is expressed in the thymus and that the levels of expression vary according to the allele class of the IDDM2 diabetes-susceptibility locus, implicating higher levels of thymic expression as being protective against autoimmune diabetes.
15. Vafiadis P, Bennett ST, Todd JA, Nadeau J, Grabs R, Goodyer CG, Wickramasinghe S, Colle E, Polychronakos C. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. of outstanding interest Nat Genet. 15:1997;289-292 This is one of two papers (with [14]) which report that the human insulin gene is expressed in the thymus and that the levels of expression vary according to the allele class of the IDDM2 diabetes-susceptibility locus, implicating higher levels of thymic expression as being protective against autoimmune diabetes. This paper also documents the presence of proinsulin protein in human thymus and assesses (in preliminary experiments) the expression in human thymus of several other candidate autoantigens.
16. Heath VL, Moore NC, Parnell SM, Mason D. Intrathymic expression of genes involved in organ specific autoimmune disease. of special interest J Autoimmun. 11:1998;309-318 This paper reports on expression of several peripheral-antigen genes, including thyroglobulin, in rat and mouse thymi.
17. Throsby M, Homo-Delarche F, Chevenne D, Goya R, Dardenne M, Pleau JM. Pancreatec hormone expression in the murine thymus: localization in dendritic cells and macrophages. of special interest Endocrinology. 139:1998;2399-2406 The authors report that proinsulin protein can be detected in mouse thymus and that the islet-cell hormone genes appear to segregate into different thymic-cell subtypes by depletion using antibody-coupled magnetic beads.
18. Grima B, Zelenika D, Pessac B. A novel transcript overlapping the myelin basic protein gene. J Neurochem. 59:1992;2318-2323.
19. Fritz RB, Zhao ML. Thymic expression of myelin basic protein (MBP). Activation of MBP-specific T cells by thymic cells in the absence of exogenous MBP. J Immunol. 157:1996;5249-5253.
20. Egwuagu CE, Charukamnoetkanok P, Gery I. Thymic expression of autoantigens correlates with resistance to autoimmune disease. of outstanding interest J Immunol. 159:1997;3109-3112 This paper reveals that strains of mice and rats differ both in their thymic expression of two retinal proteins and in their propensity to the experimental autoimmune uveoretinitis induced by those proteins, such that comparatively high thymic expression confers resistance whereas absent/lower levels correlate with susceptibility to autoimmunity.
21. Kojima K, Reindl M, Lassmann H, Wekerle H, Linington C. The thymus and self-tolerance: co-existence of encephalitogenic S100 beta-specific T cells and their nominal autoantigen in the normal adult rat thymus. of special interest Int Immunol. 9:1997;897-904 This documents the expression of a nervous-system protein in thymic stroma and reports a limited tolerizing capability of thymic expression, which can be overruled by experimental immunization.
22. Crisa L, McMaster MT, Ishii JK, Fisher SJ, Salomon DR. Identification of a thymic epithelial cell subset sharing expression of the class Ib HLA-G molecule with fetal trophoblasts. of special interest J Exp Med. 186:1998;289-298 The authors demonstrate the expression of a trophoblast-specific gene product, HLA-G, in thymus - predominantly in medullary epithelial cells.
23. Klein L, Klein T, Tuther U, Kyewski BL. CD4 T cell tolerance to human C-reactive protein, an inducible serum protein, is mediated by medullary thymic epithelium. of outstanding interest J Exp Med. 188:1998;5-16 The authors report on the expression of two liver acute-phase genes in thymus; they document, using embryonic day 15 (E15) thymus transplantation or bone marrow reconstitution, that a human C-reactive protein transgene can transfer tolerance to the human protein if expressed in the context of E15 thymus but not via the bone marrow.
24. Smith KM, Olson DC, Hirose R, Hanahan D. Pancreatic gene expression in rare cells of thymic medulla: evidence for functional contribution to T cell tolerance. of outstanding interest Int Immunol. 9:1997;1355-1365 The authors visualize the insulin-PAE cells in the thymic medulla, quantitate their relative rarity and document the functional significance of thymic expression of an insulin-promoter transgene (RIP - Tag) following thymic transplantation from neonatal transgenic mice into nontransgenic athymic recipients.
25. Pugliese A, Revann T, Zeller M, Patel DD, Ricordi C. Proinsulin-expressing cells in the human thymus. Diabetes Suppl. 47:1998;A204.
26. Sponaas AM, Tomlinson PD, Antoniou J, Auphan N, Langlet C, Malissen B, Schmitt-Verhulst AM, Mellor AL. Induction of tolerance to self MHC class I molecules expressed under the control of milk protein or beta-globin gene promoters. Int Immunol. 6:1994;277-287.
27. Förster I, Leiberam I. Peripheral tolerance of CD4 T cells following local activation in adolescent mice. Eur J Immunol. 26:1996;3194-3202.
28. Adams T, Alpert S, Hanahan D. Non-tolerance and autoantibodies to a transgenic self antigen expressed in pancreatic B-cells. Nature. 325:1987;223-228.
29. Schonrich G, Momburg F, Hammerling GJ, Arnold B. Anergy induced by thymic medullary epithelium. Eur J Immunol. 22:1992;1687-1691.
30. Hoffmann MW, Allison J, Miller JF. Tolerance induction by thymic medullary epithelium. Proc Natl Acad Sci USA. 89:1992;2526-2530.
31. Oukka M, Colucci-Guyon E, Tran PL, Cohen-Tannoudji M, Babinet C, Lotteau V, Kosmatopoulos K. CD4 T cell tolerance to nuclear proteins induced by medullary thymic epithelium. Immunity. 4:1996;545-553.
32. Farr AG, Rudensky A. Medullary thymic epithelium: a mosaic of epithelial "self"? of special interest J Exp Med. 188:1998;1-4 This provides a recent perspective on thymic expression of peripheral-antigen genes.
33. Werdelin O, Cordes U, Jensen T. Aberrant expression of tissue-specific proteins in the thymus: a hypothesis for the development of central tolerance. Scand J Immunol. 47:1998;95-100.
34. Salmon AM, Bruand C, Cardona A, Changeux JP, Berrih-Aknin S. An acetylcholine receptor alpha subunit promoter confers intrathymic expression in transgenic mice. Implications for tolerance of a transgenic self-antigen and for autoreactivity in myasthenia gravis. of special interest J Clin Invest. 101:1998;2340-2350 This paper confirms a large body of previous work suggesting that the AChR gene was expressed in thymus and thymic tumors; the authors exploit the neo-self-antigen β-gal and its reporter activity to evaluate thymic cell expression and self-tolerance induction.
35. Mombaerts P, Wang F, Dulac C, Vassar R, Chao SK, Nemes A, Mendelsohn M, Edmondson J, Axel R. The molecular biology of olfactory perception. Cold Spring Harbor Symp. 61:1996;135-145.
36. French MB, Allison J, Cram DS, Thomas HE, Dempsey-Collier M, Silva A, Georgi HM, Kay TM, Harrison LC, Lew AM. Transgenic expression of mouse proinsulin II prevents dibetes in nonobese diabetic mice. Diabetes. 46:1998;34-39.