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  • 1
    Shevach, E. M., From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity 2006 25: 195201.
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    Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J. L., Farr, A. G. and Rudensky, A. Y., Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005 22: 329341.
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    Gavin, M. A., Rasmussen, J. P., Fontenot, J. D., Vasta, V., Manganiello, V. C., Beavo, J. A. and Rudensky, A. Y., Foxp3-dependent programme of regulatory T-cell differentiation. Nature 2007 445: 771775.
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    Williams, L. M. and Rudensky, A. Y., Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat. Immunol. 2007 8: 277284.
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    Brunkow, M. E., Jeffery, E. W., Hjerrild, K. A., Paeper, B., Clark, L. B., Yasayko, S. A., Wilkinson, J. E. et al., Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 2001 27: 6873.
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    Bennett, C. L., Christie, J., Ramsdell, F., Brunkow, M. E., Ferguson, P. J., Whitesell, L., Kelly, T. E. et al., The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 2001 27: 2021.
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    Lahl, K., Loddenkemper, C., Drouin, C., Freyer, J., Arnason, J., Eberl, G., Hamann, A. et al., Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J. Exp. Med. 2007 204: 5763.
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    Kim, J. M., Rasmussen, J. P. and Rudensky, A. Y., Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 2007 8: 191197.
  • 9
    Fontenot, J. D., Gavin, M. A. and Rudensky, A. Y., Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 2003 4: 330336.
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    Hori, S., Nomura, T. and Sakaguchi, S., Control of regulatory T cell development by the transcription factor Foxp3. Science 2003 299: 10571061.
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    Wan, Y. Y. and Flavell, R. A., Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc. Natl. Acad. Sci. USA 2005 102: 51265131.
  • 12
    Walker, M. R., Kasprowicz, D. J., Gersuk, V. H., Benard, A., Van Landeghen, M., Buckner, J. H. and Ziegler, S. F., Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25 T cells. J. Clin. Invest. 2003 112: 14371443.
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    Morgan, M. E., van Bilsen, J. H., Bakker, A. M., Heemskerk, B., Schilham, M. W., Hartgers, F. C., Elferink, B. G. et al., Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans. Hum. Immunol. 2005 66: 1320.
  • 14
    Wang, J., Ioan-Facsinay, A., van der Voort, E. I. H., Huizinga, T. W. J. and Toes, R. E. M., Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur. J. Immunol. 2007 37: 129138.
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    Pillai, V., Ortega, S. B., Wang, C. K. and Karandikar, N. J., Transient regulatory T-cells: A state attained by all activated human T-cells. Clin. Immunol. 2007 123: 1829.
  • 16
    Allan, S. E., Crome, S. Q., Crellin, N. K., Passerini, L., Steiner, T. S., Bacchetta, R., Roncarolo, M. G. and Levings, M. K., Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int. Immunol. 2007 19: 345354.
  • 17
    Tran, D. Q., Ramsey, H. and Shevach, E. M., Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T cell receptor stimulation is TGF-beta-dependent but does not confer a regulatory phenotype. Blood 2007 110: 29832990.
  • 18
    Fontenot, J. D., Dooley, J. L., Farr, A. G. and Rudensky, A. Y., Developmental regulation of Foxp3 expression during ontogeny. J. Exp. Med. 2005 202: 901906.
  • 19
    Apostolou, I. and von Boehmer, H., In vivo instruction of suppressor commitment in naive T cells. J. Exp. Med. 2004 199: 14011408.
  • 20
    Kretschmer, K., Apostolou, I., Hawiger, D., Khazaie, K., Nussenzweig, M. C. and von Boehmer, H., Inducing and expanding regulatory T cell populations by foreign antigen. Nat. Immunol. 2005 12: 12191227.
  • 21
    Siewert, C., Lauer, U., Cording, S., Bopp, T., Schmitt, E., Hamann, A. and Huehn, J., Experience-driven development: effector/memory-like αE+Foxp3+ regulatory T cells originate from both naïve T cells and naturally occurring naïve-like regulatory T cells. J. Immunol. 2008 180: 146155.
  • 22
    Wong, J., Mathis, D. and Benoist, C., TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets. J. Exp. Med. 2007 204: 20392045.
  • 23
    Sun, C. M., Hall, J. A., Blank, R. B., Bouladoux, N., Oukka, M., Mora, J. R. and Belkaid, Y., Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J. Exp. Med. 2007 204: 17751785.
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    Coombes, J. L., Siddiqui, K. R., Arancibia-Carcamo, C. V., Hall, J., Sun, C. M., Belkaid, Y. and Powrie, F., A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J. Exp. Med. 2007 204: 17571764.
  • 25
    von Boehmer, H., Oral tolerance: is it all retinoic acid? J. Exp. Med. 2007 204: 17371739.
  • 26
    Chen, W., Jin, W., Hardegen, N., Lei, K. J., Li, L., Marinos, N., McGrady, G. and Wahl, S. M., Conversion of peripheral CD4+CD25 naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med. 2003 198: 18751886.
  • 27
    Fantini, M. C., Becker, C., Monteleone, G., Pallone, F., Galle, P. R. and Neurath, M. F., Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25 T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 2004 172: 51495153.
  • 28
    Fantini, M. C., Becker, C., Tubbe, I., Nikolaev, A., Lehr, H. A., Galle, P. R. and Neurath, M. F., TGF-beta induced Foxp3+ regulatory T cells suppress Th1-mediated experimental colitis. Gut 2006 55: 671680.
  • 29
    DiPaolo, R. J., Brinster, C., Davidson, T. S., Andersson, J., Glass, D. and Shevach, E. M., Autoantigen-specific TGFbeta-induced Foxp3+ regulatory T cells prevent autoimmunity by inhibiting dendritic cells from activating autoreactive T cells. J. Immunol. 2007 179: 46854693.
  • 30
    Floess, S., Freyer, J., Siewert, C., Baron, U., Olek, S., Polansky, J., Schlawe, K. et al., Epigenetic control of the foxp3 locus in regulatory T cells. PLOS Biol. 2007 5: e38.
  • 31
    Lee, G. R., Kim, S. T., Spilianakis, C. G., Fields, P. E. and Flavell, R. A., T helper cell differentiation: regulation by cis elements and epigenetics. Immunity 2006 24: 369379.
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    Kioussis, D. and Georgopoulos, K., Epigenetic flexibility underlying lineage choices in the adaptive immune system. Science 2007 317: 620622.
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    Ansel, K. M., Djuretic, I., Tanasa, B. and Rao, A., Regulation of Th2 differentiation and Il4 locus accessibility. Annu. Rev. Immunol. 2006 24: 607656.
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    Lee, D. U., Agarwal, S. and Rao, A., Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene. Immunity 2002 16: 649660.
  • 35
    Lohning, M., Richter, A., Stamm, T., Hu-Li, J., Assenmacher, M., Paul, W. E. and Radbruch, A., Establishment of memory for IL-10 expression in developing T helper 2 cells requires repetitive IL-4 costimulation and does not impair proliferation. Proc. Natl. Acad. Sci. USA 2003 100: 1230712312.
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    Chang, H. D., Helbig, C., Tykocinski, L., Kreher, S., Koeck, J., Niesner, U. and Radbruch, A., Expression of IL-10 in Th memory lymphocytes is conditional on IL-12 or IL-4, unless the IL-10 gene is imprinted by GATA-3. Eur. J. Immunol. 2007 37: 807817.
  • 37
    Creusot, F., Acs, G. and Christman, J. K., Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-azacytidine and 5-aza-2′-deoxycytidine. J. Biol. Chem. 1982 257: 20412048.
  • 38
    Selvaraj, R. K. and Geiger, T. L., A kinetic and dynamic analysis of Foxp3 induced in T cells by TGF-beta. J. Immunol. 2007 179: 13901401.
  • 39
    Kretschmer, K., Heng, T. S. and von Boehmer, H., De novo production of antigen-specific suppressor cells in vivo. Nat. Protoc. 2006 1: 653661.
  • 40
    Mantel, P. Y., Ouaked, N., Ruckert, B., Karagiannidis, C., Welz, R., Blaser, K. and Schmidt-Weber, C. B., Molecular mechanisms underlying FOXP3 induction in human T cells. J. Immunol. 2006 176: 35933602.
  • 41
    Zorn, E., Nelson, E. A., Mohseni, M., Porcheray, F., Kim, H., Litsa, D., Bellucci, R. et al., IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT dependent mechanism and induces the expansion of these cells in vivo. Blood 2006 108: 15711579.
  • 42
    Baron, U., Floess, S., Wieczorek, G., Baumann, K., Grützkau, A., Dong, J., Thiel, A. et al., DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells. Eur. J. Immunol. 2007 37: 23782389.
  • 43
    Kim, H. P. and Leonard, W. J., CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J. Exp. Med. 2007 204: 15431551.
  • 44
    Park, H. B., Paik, D. J., Jang, E., Hong, S. and Youn, J., Acquisition of anergic and suppressive activities in transforming growth factor-beta-costimulated CD4+CD25 T cells. Int. Immunol. 2004 16: 12031213.
  • 45
    Benson, M. J., Pino-Lagos, K., Rosemblatt, M. and Noelle, R. J., All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J. Exp. Med. 2007 204: 17651774.
  • 46
    Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M. and Cheroutre, H., Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007 317: 256260.
  • 47
    Kang, S. G., Lim, H. W., Andrisani, O. M., Broxmeyer, H. E. and Kim, C. H., Vitamin A metabolites induce gut-homing FoxP3+ regulatory T cells. J. Immunol. 2007 179: 37243733.
  • 48
    Grueter, B., Petter, M., Egawa, T., Laule-Kilian, K., Aldrian, C. J., Wuerch, A., Ludwig, Y. et al., Runx3 regulates integrin alpha E/CD103 and CD4 expression during development of CD4/CD8+ T cells. J. Immunol. 2005 175: 16941705.