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Mediators of Inflammation
Volume 2016, Article ID 9523628, 16 pages
http://dx.doi.org/10.1155/2016/9523628
Review Article

Thymic and Postthymic Regulation of Naïve CD4+ T-Cell Lineage Fates in Humans and Mice Models

1Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil
2Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil

Received 8 January 2016; Accepted 28 April 2016

Academic Editor: Nicola Gagliani

Copyright © 2016 José E. Belizário et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Y. Zheng and A. Y. Rudensky, “Foxp3 in control of the regulatory T cell lineage,” Nature Immunology, vol. 8, no. 5, pp. 457–462, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. T. Graf and T. Enver, “Forcing cells to change lineages,” Nature, vol. 462, no. 7273, pp. 587–594, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. V. Appay, A. Bosio, S. Lokan et al., “Sensitive gene expression profiling of human T cell subsets reveals parallel post-thymic differentiation for CD4+ and CD8+ lineages,” The Journal of Immunology, vol. 179, no. 11, pp. 7406–7414, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. T. Boehm and C. C. Bleul, “The evolutionary history of lymphoid organs,” Nature Immunology, vol. 8, no. 2, pp. 131–135, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. P. J. Fink, “The biology of recent thymic emigrants,” Annual Review of Immunology, vol. 31, pp. 31–50, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. C. C. Blackburn and N. R. Manley, “Developing a new paradigm for thymus organogenesis,” Nature Reviews Immunology, vol. 4, no. 4, pp. 278–289, 2004. View at Publisher · View at Google Scholar · View at Scopus
  7. Y. Xing and K. A. Hogquist, “T-cell tolerance: central and peripheral,” Cold Spring Harbor Perspectives in Biology, vol. 4, no. 6, Article ID a006957, 2012. View at Publisher · View at Google Scholar
  8. S. J. Sohn, J. Thompson, and A. Winoto, “Apoptosis during negative selection of autoreactive thymocytes,” Current Opinion in Immunology, vol. 19, no. 5, pp. 510–515, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. C.-S. Hsieh, H.-M. Lee, and C.-W. J. Lio, “Selection of regulatory T cells in the thymus,” Nature Reviews Immunology, vol. 12, no. 3, pp. 157–167, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. T. Egawa, “Runx and ThPOK: a balancing act to regulate thymocyte lineage commitment,” Journal of Cellular Biochemistry, vol. 107, no. 6, pp. 1037–1045, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. X. He, K. Park, and D. J. Kappes, “The role of ThPOK in control of CD4/CD8 lineage commitment,” Annual Review of Immunology, vol. 28, pp. 295–320, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. M. A. Luckey, M. Y. Kimura, A. T. Waickman, L. Feigenbaum, A. Singer, and J.-H. Park, “The transcription factor ThPOK suppresses Runx3 and imposes CD4+ lineage fate by inducing the SOCS suppressors of cytokine signaling,” Nature Immunology, vol. 15, no. 7, pp. 638–645, 2014. View at Publisher · View at Google Scholar · View at Scopus
  13. T. R. Mosmann and R. L. Coffman, “TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties,” Annual Review of Immunology, vol. 7, pp. 145–173, 1989. View at Publisher · View at Google Scholar · View at Scopus
  14. A. O'Garra, “Cytokines induce the development of functionally heterogeneous T helper cell subsets,” Immunity, vol. 8, no. 3, pp. 275–283, 1998. View at Publisher · View at Google Scholar · View at Scopus
  15. A. O'Garra and P. Vieira, “TH1 cells control themselves by producing interleukin-10,” Nature Reviews Immunology, vol. 7, no. 6, pp. 425–428, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. D. R. Littman and A. Y. Rudensky, “Th17 and regulatory T cells in mediating and restraining inflammation,” Cell, vol. 140, no. 6, pp. 845–858, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. A. S. Weinmann, “Regulatory mechanisms that control T-follicular helper and T-helper 1 cell flexibility,” Immunology and Cell Biology, vol. 92, no. 1, pp. 34–39, 2014. View at Publisher · View at Google Scholar · View at Scopus
  18. S. L. Reiner, F. Sallusto, and A. Lanzavecchia, “Division of Labor with a workforce of one: challenges in specifying effector and memory T cell fate,” Science, vol. 317, no. 5838, pp. 622–625, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Sakaguchi and F. Powrie, “Emerging challenges in regulatory T cell function and biology,” Science, vol. 317, no. 5838, pp. 627–629, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. L. Zhou, M. M. W. Chong, and D. R. Littman, “Plasticity of CD4+ T cell lineage differentiation,” Immunity, vol. 30, no. 5, pp. 646–655, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. T. Hong, J. Xing, L. Li, and J. J. Tyson, “A simple theoretical framework for understanding heterogeneous differentiation of CD4+ T cells,” BMC Systems Biology, vol. 6, article 66, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. S. M. Wahl and W. Chen, “Transforming growth factor-β-induced regulatory T cells referee inflammatory and autoimmune diseases,” Arthritis Research and Therapy, vol. 7, no. 2, pp. 62–68, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. S. Romagnani, E. Maggi, F. Liotta, L. Cosmi, and F. Annunziato, “Properties and origin of human Th17 cells,” Cellular Immunology, vol. 47, no. 1, pp. 3–7, 2009. View at Publisher · View at Google Scholar
  24. L. Gorelik and R. A. Flavell, “Abrogation of TGFβ signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease,” Immunity, vol. 12, no. 2, pp. 171–181, 2000. View at Publisher · View at Google Scholar · View at Scopus
  25. W. Chen, W. Jin, N. Hardegen et al., “Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3,” The Journal of Experimental Medicine, vol. 198, no. 12, pp. 1875–1886, 2003. View at Google Scholar
  26. F. Annunziato, L. Cosmi, V. Santarlasci et al., “Phenotypic and functional features of human Th17 cells,” The Journal of Experimental Medicine, vol. 204, no. 8, pp. 1849–1861, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. J. J. O'Shea, S. M. Steward-Tharp, A. Laurence et al., “Signal transduction and Th17 cell differentiation,” Microbes and Infection, vol. 11, no. 5, pp. 599–611, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. E. Jaensson, H. Uronen-Hansson, O. Pabst et al., “Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans,” The Journal of Experimental Medicine, vol. 205, no. 9, pp. 2139–2149, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. D. Mucida, Y. Park, G. Kim et al., “Reciprocal Th17 and regulatory T cell differentiation mediated by retinoic acid,” Science, vol. 317, no. 5835, pp. 256–260, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. Y. Iwakura and H. Ishigame, “The IL-23/IL-17 axis in inflammation,” The Journal of Clinical Investigation, vol. 116, no. 5, pp. 1218–1222, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. J. P. S. Peron, A. P. Ligeiro de Oliveira, and L. V. Rizzo, “It takes guts for tolerance: the phenomenon of oral tolerance and the regulation of autoimmune response,” Autoimmunity Reviews, vol. 9, no. 1, pp. 1–4, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. L. Zhou, J. E. Lopes, M. M. Chong et al., “TGF-beta-induced Foxp3 inhibits Th17 cell differentiation by antagonizing RORγt function,” Nature, vol. 453, no. 7192, pp. 236–240, 2008. View at Google Scholar
  33. D. A. A. Vignali, L. W. Collison, and C. J. Workman, “How regulatory T cells work,” Nature Reviews Immunology, vol. 8, no. 7, pp. 523–532, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. M. J. McGeachy, Y. Chen, C. M. Tato et al., “The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo,” Nature Immunology, vol. 10, no. 3, pp. 314–324, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. M. J. McGeachy, K. S. Bak-Jensen, Y. Chen et al., “TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology,” Nature Immunology, vol. 8, no. 12, pp. 1390–1397, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. G. H. Stummvoll, R. J. DiPaolo, E. N. Huter et al., “Th1, Th2, and Th17 effector T cell-induced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells,” The Journal of Immunology, vol. 181, no. 3, pp. 1908–1916, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Louten, K. Boniface, and R. de Waal Malefyt, “Development and function of TH17 cells in health and disease,” Journal of Allergy and Clinical Immunology, vol. 123, no. 5, pp. 1004–1011, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. E. V. Acosta-Rodriguez, G. Napolitani, A. Lanzavecchia, and F. Sallusto, “Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells,” Nature Immunology, vol. 8, no. 9, pp. 942–949, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. N. Gagliani, M. C. Vesely, A. Iseppon et al., “Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation,” Nature, vol. 523, no. 7559, pp. 221–225, 2015. View at Publisher · View at Google Scholar
  40. M. Veldhoen, C. Uyttenhove, J. van Snick et al., “Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset,” Nature Immunology, vol. 9, pp. 1341–1346, 2008. View at Google Scholar
  41. M. Stassen, E. Schmitt, and T. Bopp, “From interleukin-9 to T helper 9 cells,” Annals of the New York Academy of Sciences, vol. 1247, no. 1, pp. 56–68, 2012. View at Publisher · View at Google Scholar · View at Scopus
  42. M. H. Kaplan, “Th9 cells: differentiation and disease,” Immunological Reviews, vol. 252, no. 1, pp. 104–115, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. E. Schmitt, M. Klein, and T. Bopp, “Th9 cells, new players in adaptive immunity,” Trends in Immunology, vol. 35, no. 2, pp. 61–68, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. P. Licona-Limón, J. Henao-Mejia, A. U. Temann et al., “Th9 cells drive host immunity against gastrointestinal worm infection,” Immunity, vol. 39, no. 4, pp. 744–757, 2013. View at Publisher · View at Google Scholar · View at Scopus
  45. N. Fazilleau, L. Mark, L. J. McHeyzer-Williams, and M. G. McHeyzer-Williams, “Follicular helper T cells: lineage and location,” Immunity, vol. 30, no. 3, pp. 324–335, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. C. S. Ma, E. K. Deenick, M. Batten, and S. G. Tangye, “The origins, function, and regulation of T follicular helper cells,” The Journal of Cell Biology, vol. 209, no. 7, pp. 1241–1253, 2012. View at Google Scholar
  47. R. J. Johnston, A. C. Poholek, D. DiToro et al., “Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation,” Science, vol. 325, no. 5943, pp. 1006–1010, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. I. Wollenberg, A. Agua-Doce, A. Hernández et al., “Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells,” The Journal of Immunology, vol. 187, no. 9, pp. 4553–4560, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. S. Sakaguchi, N. Sakaguchi, M. Asano, M. Itoh, and M. Toda, “Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases,” The Journal of Immunology, vol. 155, no. 3, pp. 1151–1164, 1995. View at Google Scholar · View at Scopus
  50. J. D. Fontenot, M. A. Gavin, and A. Y. Rudensky, “Foxp3 programs the development and function of CD4+CD25+ regulatory T cells,” Nature Immunology, vol. 4, no. 4, pp. 330–336, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. M. A. Gavin, J. P. Rasmussen, J. D. Fontenot et al., “Foxp3-dependent programme of regulatory T-cell differentiation,” Nature, vol. 445, no. 7129, pp. 771–775, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. M. A. Linterman, W. Pierson, S. K. Lee et al., “Foxp3+ follicular regulatory T cells control the germinal center response,” Nature Medicine, vol. 17, no. 8, pp. 975–982, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Benoist and D. Mathis, “Treg cells, life history, and diversity,” Cold Spring Harbor Perspectives in Biology, vol. 4, Article ID a007021, 2012. View at Google Scholar · View at Scopus
  54. Q. Jiang, H. Su, G. Knudsen, W. Helms, and L. Su, “Delayed functional maturation of natural regulatory T cells in the medulla of postnatal thymus: role of TSLP,” BMC Immunology, vol. 7, article 6, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Sakaguchi, K. Wing, Y. Onishi, P. Prieto-Martin, and T. Yamaguchi, “Regulatory T cells: how do they suppress immune responses?” International Immunology, vol. 21, no. 10, pp. 1105–1111, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. D. Mucida, Y. Park, and H. Cheroutre, “From the diet to the nucleus: Vitamin A and TGF-β join efforts at the mucosal interface of the intestine,” Seminars in Immunology, vol. 21, no. 1, pp. 14–21, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Amarnath, C. M. Costanzo, J. Mariotti et al., “Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1,” PLoS Biology, vol. 8, no. 2, Article ID e1000302, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. E. M. Shevach, “Mechanisms of Foxp3+ T regulatory cell-mediated suppression,” Immunity, vol. 30, no. 5, pp. 636–645, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. M. O. Li, S. Sanjabi, and R. A. Flavell, “Transforming growth factor-β controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms,” Immunity, vol. 25, no. 3, pp. 455–471, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. Y. Liu, P. Zhang, J. Li, A. B. Kulkarni, S. Perruche, and W. Chen, “A critical function for TGF-β signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells,” Nature Immunology, vol. 9, no. 6, pp. 632–640, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. M. Kleinewietfeld and D. A. Hafler, “Regulatory T cells in autoimmune neuroinflammation,” Immunological Reviews, vol. 259, no. 1, pp. 231–244, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. X. Cao, S. F. Cai, T. A. Fehniger et al., “Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance,” Immunity, vol. 27, no. 4, pp. 635–646, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. T. Bopp, C. Becker, M. Klein et al., “Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression,” Journal of Experimental Medicine, vol. 204, no. 6, pp. 1303–1310, 2007. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Deaglio, K. M. Dwyer, W. Gao et al., “Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression,” Journal of Experimental Medicine, vol. 204, no. 6, pp. 1257–1265, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. M. F. Murray, “The human indoleamine 2,3-dioxygenase gene and related human genes,” Current Drug Metabolism, vol. 8, no. 3, pp. 197–200, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. J. D. Mezrich, J. H. Fechner, X. Zhang, B. P. Johnson, W. J. Burlingham, and C. A. Bradfield, “An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells,” The Journal of Immunology, vol. 185, no. 6, pp. 3190–3198, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. F. J. Quintana, A. S. Basso, A. H. Iglesias et al., “Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor,” Nature, vol. 453, no. 7191, pp. 65–71, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Battaglia, S. Gregori, R. Bacchetta, and M.-G. Roncarolo, “Tr1 cells: from discovery to their clinical application,” Seminars in Immunology, vol. 18, no. 2, pp. 120–127, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. A. M. Thornton, P. E. Korty, D. Q. Tran et al., “Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells,” Journal of Immunology, vol. 184, no. 7, pp. 3433–3441, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. C. Pot, L. Apetoh, and V. K. Kuchroo, “Type 1 regulatory T cells (Tr1) in autoimmunity,” Seminars in Immunology, vol. 23, no. 3, pp. 202–208, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. H. Jonuleit, E. Schmitt, G. Schuler, J. Knop, and A. H. Enk, “Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells,” The Journal of Experimental Medicine, vol. 192, no. 9, pp. 1213–1222, 2000. View at Publisher · View at Google Scholar · View at Scopus
  72. H. Jonuleit and E. Schmitt, “The regulatory T cell family: distinct subsets and their interrelations,” The Journal of Immunology, vol. 171, no. 12, pp. 6323–6327, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. Chen, V. K. Kuchroo, J.-I. Inobe, J. D. A. Hafler, and H. L. Weiner, “Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis,” Science, vol. 265, no. 5176, pp. 1237–1240, 1994. View at Publisher · View at Google Scholar · View at Scopus
  74. J. Y. Niederkorn, “Emerging concepts in CD8+ T regulatory cells,” Current Opinion in Immunology, vol. 20, no. 3, pp. 327–331, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. P. Hoffmann, J. Ermann, M. Edinger, C. G. Fathman, and S. Strober, “Donor-type CD4+CD25+ regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation,” The Journal of Experimental Medicine, vol. 196, no. 3, pp. 389–399, 2002. View at Publisher · View at Google Scholar
  76. X. L. Li, S. Ménoret, S. Bezie et al., “Mechanism and localization of CD8 regulatory T cells in a heart transplant model of tolerance,” The Journal of Immunology, vol. 185, no. 2, pp. 823–833, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. C. L. Bennett, J. Christie, F. Ramsdell et al., “The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3,” Nature Genetics, vol. 27, no. 1, pp. 20–21, 2001. View at Publisher · View at Google Scholar · View at Scopus
  78. R. S. Wildin, F. Ramsdell, J. Peake et al., “X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy,” Nature Genetics, vol. 27, no. 1, pp. 18–20, 2001. View at Publisher · View at Google Scholar · View at Scopus
  79. M. E. Brunkow, E. W. Jeffery, K. A. Hjerrild et al., “Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse,” Nature Genetics, vol. 27, no. 1, pp. 68–73, 2001. View at Publisher · View at Google Scholar · View at Scopus
  80. X. Chang, J. X. Gao, Q. Jiang et al., “The Scurfy mutation of FoxP3 in the thymus stroma leads to defective thymopoiesis,” The Journal of Experimental Medicine, vol. 202, no. 8, pp. 1141–1151, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. Q. Tang and J. A. Bluestone, “Regulatory T-cell therapy in transplantation: moving to the clinic,” Cold Spring Harbor Perspectives in Medicine, vol. 3, no. 11, Article ID a015552, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. T. A. Q. Baldwin, T. K. Starr, and K. A. Hogquist, “Mouse models of negative selection,” in The Mouse in Biomedical Research, J. M. Fox, S. Barthold, M. Davisson, C. E. Newcomer, F. W. Quimby, and A. Smith, Eds., pp. 303–313, Academic Press, Burlington, Mass, USA, 2nd edition, 2007. View at Google Scholar
  83. V. Heissmeyer, B. Tanasa, and A. Rao, “Peripheral tolerance of T cells in the mouse,” in The Mouse in Biomedical Research, J. M. Fox, S. Barthold, M. Davisson, C. E. Newcomer, F. W. Quimby, and A. Smith, Eds., pp. 223–242, Academic Press, Burlington, Mass, USA, 2nd edition, 2007. View at Google Scholar
  84. J. E. Belizario, “Immunodeficient mouse models: an overview,” The Open Immunology Journal, vol. 2, no. 1, pp. 79–85, 2009. View at Publisher · View at Google Scholar
  85. F. Miyagawa, J. Gutermuth, H. Zhang, and S. I. Katz, “The use of mouse models to better understand mechanisms of autoimmunity and tolerance,” Journal of Autoimmunity, vol. 35, no. 3, pp. 192–198, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. L. D. Shultz, N. Goodwin, F. Ishikawa, V. Hosur, B. L. Lyons, and D. L. Greiner, “Human cancer growth and therapy in immunodeficient mouse models,” Cold Spring Harbor Protocols, vol. 2014, no. 7, pp. 694–708, 2014. View at Publisher · View at Google Scholar · View at Scopus
  87. E. K. Colvin, C. Weir, R. J. Ikin, and A. L. Hudson, “SV40 TAg mouse models of cancer,” Seminars in Cell and Developmental Biology, vol. 27, pp. 61–73, 2014. View at Publisher · View at Google Scholar · View at Scopus
  88. C. Koble and B. Kyewski, “The thymic medulla: a unique microenvironment for intercellular self-antigen transfer,” Journal of Experimental Medicine, vol. 206, no. 7, pp. 1505–1513, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. M. S. Anderson, E. S. Venanzi, Z. Chen, S. P. Berzins, C. Benoist, and D. Mathis, “The cellular mechanism of Aire control of T cell tolerance,” Immunity, vol. 23, no. 2, pp. 227–239, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. G. O. Gillard, J. Dooley, M. Erickson, L. Peltonen, and A. G. Farr, “Aire-dependent alterations in medullary thymic epithelium indicate a role for Aire in thymic epithelial differentiation,” The Journal of Immunology, vol. 178, no. 5, pp. 3007–3015, 2007. View at Publisher · View at Google Scholar · View at Scopus
  91. M. S. Anderson and M. A. Su, “Aire and T cell development,” Current Opinion in Immunology, vol. 23, no. 2, pp. 198–206, 2011. View at Publisher · View at Google Scholar
  92. C. C. Blackburn, C. L. Augustine, R. Li et al., “The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 12, pp. 5742–5746, 1996. View at Publisher · View at Google Scholar · View at Scopus
  93. Z. Zhang, P. Burnley, B. Coder, and D.-M. Su, “Insights on Foxn1 biological significance and usages of the ‘nude’ mouse in studies of T-Lymphopoiesis,” International Journal of Biological Sciences, vol. 8, no. 8, pp. 1156–1167, 2012. View at Publisher · View at Google Scholar · View at Scopus
  94. M. Kasai, E. Kominami, and T. Mizuochi, “The antigen presentation pathway in medullary thymic epithelial cells, but not that in cortical thymic epithelial cells, conforms to the endocytic pathway,” European Journal of Immunology, vol. 28, no. 6, pp. 1867–1876, 1998. View at Publisher · View at Google Scholar · View at Scopus
  95. D. Capalbo, G. Giardino, L. D. Martino et al., “Genetic basis of altered central tolerance and autoimmune diseases: a lesson from AIRE mutations,” International Reviews of Immunology, vol. 31, no. 5, pp. 344–362, 2012. View at Publisher · View at Google Scholar · View at Scopus
  96. J. Aaltonen, P. Björses, J. Perheentupa et al., “An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains,” Nature Genetics, vol. 17, no. 4, pp. 399–403, 1997. View at Publisher · View at Google Scholar · View at Scopus
  97. A. R. Bennett, A. Farley, N. F. Blair, J. Gordon, L. Sharp, and C. C. Blackburn, “Identification and characterization of thymic epithelial progenitor cells,” Immunity, vol. 16, no. 6, pp. 803–814, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. S. P. Flanagan, “‘Nude’, a new hairless gene with pleiotropic effects in the mouse,” Genetical Research, vol. 8, no. 3, pp. 295–309, 1966. View at Publisher · View at Google Scholar · View at Scopus
  99. C. Pignata, M. Fiore, V. Guzzetta et al., “Congenital alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs,” American Journal of Medical Genetics, vol. 65, no. 2, pp. 167–170, 1996. View at Publisher · View at Google Scholar · View at Scopus
  100. H.-R. Rodewald, “Thymus organogenesis,” Annual Review of Immunology, vol. 26, pp. 355–388, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. N. R. Manley, E. R. Richie, C. C. Blackburn, B. G. Condie, and J. Sage, “Structure and function of the thymic microenvironment,” Frontiers in Bioscience, vol. 16, no. 7, pp. 2461–2477, 2011. View at Publisher · View at Google Scholar · View at Scopus
  102. H. E. Lynch, G. L. Goldberg, A. Chidgey, M. R. M. Van den Brink, R. Boyd, and G. D. Sempowski, “Thymic involution and immune reconstitution,” Trends in Immunology, vol. 30, no. 7, pp. 366–373, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. P. L. F. Johnson, A. J. Yates, J. J. Goronzy, and R. Antia, “Peripheral selection rather than thymic involution explains sudden contraction in naive CD4 T-cell diversity with age,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 52, pp. 21432–21437, 2012. View at Publisher · View at Google Scholar · View at Scopus
  104. G. A. Holländer, W. Krenger, and B. R. Blazar, “Emerging strategies to boost thymic function,” Current Opinion in Pharmacology, vol. 10, no. 4, pp. 443–453, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. G. D. Sempowski, L. P. Hale, J. S. Sundy et al., “Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy,” The Journal of Immunology, vol. 164, no. 4, pp. 2180–2187, 2000. View at Publisher · View at Google Scholar · View at Scopus
  106. A. V. Griffith, M. Fallahi, T. Venables, and H. T. Petrie, “Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth,” Aging Cell, vol. 11, no. 1, pp. 169–177, 2012. View at Publisher · View at Google Scholar · View at Scopus
  107. P. S. Jat, M. D. Noble, P. Ataliotis et al., “Direct derivation of conditionally immortal cell lines from an H-2Kb-tsA58 transgenic mouse,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 12, pp. 5096–5100, 1991. View at Publisher · View at Google Scholar · View at Scopus
  108. G. Kern and B. E. Flucher, “Localization of transgenes and genotyping of H-2Kb-tsA58 transgenic mice,” BioTechniques, vol. 38, no. 1, pp. 38–42, 2005. View at Publisher · View at Google Scholar · View at Scopus
  109. A. C. Custodio, F. C. F. Brito, M. S. Junqueira, R. Chammas, and J. E. Belizario, “Genotype and phenotype of Balb/c mouse strain expressing H-2Kb-tsA58-SV40 immortalizing oncogene,” BMC Cancer Proceedings, vol. 7, supplement 2, article P3, 2013. View at Google Scholar
  110. M. Noble, A. Groves, P. Ataliotis, Z. Ikram, and P. Jat, “The H-2KbtsA58 transgenic mouse: a new toll for the rapid generation of novel cell lines,” Transgenic Research, vol. 4, no. 4, pp. 215–225, 1995. View at Publisher · View at Google Scholar
  111. M. Obinata, “The immortalized cell lines with differentiation potentials: their establishment and possible application,” Cancer Science, vol. 98, no. 3, pp. 275–283, 2007. View at Publisher · View at Google Scholar · View at Scopus
  112. J. M. Pipas, “SV40: cell transformation and tumorigenesis,” Virology, vol. 384, no. 2, pp. 294–303, 2009. View at Publisher · View at Google Scholar · View at Scopus
  113. P. An, M. T. Sáenz-Robles, and J. M. Pipas, “Large T antigens of polyomaviruses: amazing molecular machines,” Annual Review of Microbiology, vol. 66, pp. 213–236, 2012. View at Publisher · View at Google Scholar · View at Scopus
  114. J. Cheng, J. A. DeCaprio, M. M. Fluck, and B. S. Schaffhausen, “Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens,” Seminars in Cancer Biology, vol. 19, no. 4, pp. 218–228, 2009. View at Publisher · View at Google Scholar · View at Scopus
  115. S. Sadasivam and J. A. DeCaprio, “The DREAM complex: master coordinator of cell cycle-dependent gene expression,” Nature Reviews Cancer, vol. 13, no. 8, pp. 585–595, 2013. View at Publisher · View at Google Scholar · View at Scopus
  116. S. Hauser, T. Ulrich, S. Wurster, K. Schmitt, N. Reichert, and S. Gaubatz, “Loss of LIN9, a member of the DREAM complex, cooperates with SV40 large T antigen to induce genomic instability and anchorage-independent growth,” Oncogene, vol. 31, no. 14, pp. 1859–1868, 2012. View at Publisher · View at Google Scholar · View at Scopus
  117. A. D. Colantonio, M. Epeldegui, M. Jesiak, L. Jachimowski, B. Blom, and C. H. Uittenbogaart, “IFN-α is constitutively expressed in the human thymus, but not in peripheral lymphoid organs,” PLoS ONE, vol. 6, no. 8, Article ID e24252, 2011. View at Publisher · View at Google Scholar · View at Scopus
  118. A. I. Robles, F. Larcher, R. B. Whalin et al., “Expression of cyclin D1 in epithelial tissues of transgenic mice results in epidermal hyperproliferation and severe thymic hyperplasia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 15, pp. 7634–7638, 1996. View at Publisher · View at Google Scholar · View at Scopus
  119. W. C. Hahn and R. A. Weinberg, “Modelling the molecular circuitry of cancer,” Nature Reviews Cancer, vol. 2, no. 5, pp. 331–341, 2002. View at Publisher · View at Google Scholar · View at Scopus
  120. J. Cheng, J. A. DeCaprio, M. M. Fluck, and B. S. Schaffhausen, “Cellular transformation by simian virus 40 and murine polyoma virus T antigens,” Seminars in Cancer Biology, vol. 19, no. 4, pp. 218–228, 2009. View at Publisher · View at Google Scholar · View at Scopus
  121. J. S. Kasper, H. Kuwabara, T. Arai, S. H. Ali, and J. A. DeCaprio, “Simian virus 40 large T antigen's association with the CUL7 SCF complex contributes to cellular transformation,” Journal of Virology, vol. 79, no. 18, pp. 11685–11692, 2005. View at Publisher · View at Google Scholar · View at Scopus
  122. A. Forero, N. S. Giacobbi, K. D. McCormick et al., “Simian virus 40 large T antigen induces IFN-stimulated genes through ATR kinase,” Journal of Immunology, vol. 192, no. 12, pp. 5933–5942, 2014. View at Publisher · View at Google Scholar · View at Scopus
  123. G. Rohaly, K. Korf, S. Dehde, and I. Dornreiter, “Simian virus 40 activates ATR-Delta p53 signaling to override cell cycle and DNA replication control,” Journal of Virology, vol. 84, no. 20, pp. 10727–10747, 2010. View at Google Scholar
  124. P. G. Cantalupo, M. T. Sáenz-Robles, A. V. Rathi et al., “Cell-type specific regulation of gene expression by simian virus 40 T antigens,” Virology, vol. 386, no. 1, pp. 183–191, 2009. View at Publisher · View at Google Scholar · View at Scopus
  125. A. V. Rathi, P. G. Cantalupo, S. N. Sarkar, and J. M. Pipas, “Induction of interferon-stimulated genes by Simian virus 40 T antigens,” Virology, vol. 406, no. 2, pp. 202–211, 2010. View at Publisher · View at Google Scholar · View at Scopus
  126. O. Gjoerup and Y. Chang, “Update on human polyomaviruses and cancer,” Advances in Cancer Research, vol. 106, pp. 1–51, 2010. View at Publisher · View at Google Scholar · View at Scopus
  127. W. J. Lu, J. F. Amatruda, and J. M. Abrams, “P53 ancestry: gazing through an evolutionary lens,” Nature Reviews Cancer, vol. 9, no. 10, pp. 758–762, 2009. View at Publisher · View at Google Scholar · View at Scopus
  128. Q. N. Hu and T. A. Baldwin, “Differential roles for Bim and Nur77 in thymocyte clonal deletion induced by ubiquitous self-antigen,” Journal of Immunology, vol. 194, no. 6, pp. 2643–2653, 2015. View at Publisher · View at Google Scholar · View at Scopus
  129. N. Bredenkamp, S. Ulyanchenko, K. E. O'Neill, N. R. Manley, H. J. Vaidya, and C. C. Blackburn, “An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts,” Nature Cell Biology, vol. 16, no. 9, pp. 902–908, 2014. View at Publisher · View at Google Scholar · View at Scopus
  130. H. S. Symonds, S. A. McCarthy, J. Chen, J. M. Pipas, and T. Van Dyke, “Use of transgenic mice reveals cell-specific transformation by a simian virus 40 T-antigen amino-terminal mutant,” Molecular and Cellular Biology, vol. 13, no. 6, pp. 3255–3265, 1993. View at Publisher · View at Google Scholar · View at Scopus
  131. S. A. McCarthy, H. S. Symonds, and T. Van dyke, “Regulation of apoptosis in transgenic mice by simian virus 40 T antigen-mediated inactivation of p53,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 9, pp. 3979–3983, 1994. View at Publisher · View at Google Scholar · View at Scopus