Plasticity of Foxp3 + T Cells Reflects Promiscuous Foxp3 Expression in Conventional T Cells but Not Reprogramming of Regulatory T Cells

Immunity

Volumn 36, Issue 2, 2012, Pages 262-275

  Miyao, Takahisa ^a   Floess, Stefan ^b   Setoguchi, Ruka ^a   Luche, Hervé ^c   Fehling, Hans Joerg ^c   Waldmann, Herman ^d   Huehn, Jochen ^b   Hori, Shohei ^a  

^a RIKEN Center for Integrative Medical Sciences   (Japan)

^b HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^c UNIVERSITY HOSPITAL ULM   (Germany)

^d UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSCRIPTION FACTOR FOXP3;

ADOPTIVE TRANSFER; ANIMAL CELL; ARTICLE; CELL LINEAGE; GENE MAPPING; HELPER CELL; LYMPHOCYTE SUBPOPULATION; MEMORY T LYMPHOCYTE; MOUSE; NONHUMAN; NUCLEAR REPROGRAMMING; NUCLEOTIDE SEQUENCE; PLASTICITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION;

ANIMALS; ANTIGENS, CD2; CD4-POSITIVE T-LYMPHOCYTES; CELL DIFFERENTIATION; CELL LINEAGE; DNA METHYLATION; EPIGENESIS, GENETIC; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION; HUMANS; IMMUNOLOGIC MEMORY; INFLAMMATION; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; LYMPHOCYTE ACTIVATION; LYMPHOPENIA; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY;

EID: 84857416489     PISSN: 10747613     EISSN: 10974180     Source Type: Journal    
DOI: 10.1016/j.immuni.2011.12.012     Document Type: Article

References (48)

1. Allan S.E., Crome S.Q., Crellin N.K., Passerini L., Steiner T.S., Bacchetta R., Roncarolo M.G., Levings M.K. Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int. Immunol. 2007, 19:345-354.
2. Bailey-Bucktrout S.L., Bluestone J.A. Regulatory T cells: stability revisited. Trends Immunol. 2011, 32:301-306.
3. Baron U., Floess S., Wieczorek G., Baumann K., Grützkau A., Dong J., Thiel A., Boeld T.J., Hoffmann P., Edinger M., et al. DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. Eur. J. Immunol. 2007, 37:2378-2389.
4. Chen W., Jin W., Hardegen N., Lei K.J., Li L., Marinos N., McGrady G., 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, 198:1875-1886.
5. Cobbold S.P., Castejon R., Adams E., Zelenika D., Graca L., Humm S., Waldmann H. Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants. J. Immunol. 2004, 172:6003-6010.
6. Curotto de Lafaille M.A., Kutchukhidze N., Shen S., Ding Y., Yee H., Lafaille J.J. Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic inflammation. Immunity 2008, 29:114-126.
7. Duarte J.H., Zelenay S., Bergman M.L., Martins A.C., Demengeot J. Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions. Eur. J. Immunol. 2009, 39:948-955.
8. Floess S., Freyer J., Siewert C., Baron U., Olek S., Polansky J., Schlawe K., Chang H.D., Bopp T., Schmitt E., et al. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 2007, 5:e38.
9. Fontenot J.D., Gavin M.A., Rudensky A.Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 2003, 4:330-336.
10. Fontenot J.D., Rasmussen J.P., Williams L.M., Dooley J.L., Farr A.G., Rudensky A.Y. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005, 22:329-341.
11. Gabor M.J., Godfrey D.I., Scollay R. Recent thymic emigrants are distinct from most medullary thymocytes. Eur. J. Immunol. 1997, 27:2010-2015.
12. Gavin M., Rudensky A. Control of immune homeostasis by naturally arising regulatory CD4+ T cells. Curr. Opin. Immunol. 2003, 15:690-696.
13. Gavin M.A., Torgerson T.R., Houston E., DeRoos P., Ho W.Y., Stray-Pedersen A., Ocheltree E.L., Greenberg P.D., Ochs H.D., Rudensky A.Y. Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc. Natl. Acad. Sci. USA 2006, 103:6659-6664.
14. Haribhai D., Williams J.B., Jia S., Nickerson D., Schmitt E.G., Edwards B., Ziegelbauer J., Yassai M., Li S.H., Relland L.M., et al. A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity. Immunity 2011, 35:109-122.
15. Hill J.A., Feuerer M., Tash K., Haxhinasto S., Perez J., Melamed R., Mathis D., Benoist C. Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 2007, 27:786-800.
16. Hori S. Developmental plasticity of Foxp3+ regulatory T cells. Curr. Opin. Immunol. 2010, 22:575-582.
17. Hori S. Regulatory T cell plasticity: beyond the controversies. Trends Immunol. 2011, 32:295-300.
18. Hori S., Nomura T., Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003, 299:1057-1061.
19. Huehn J., Polansky J.K., Hamann A. Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage?. Nat. Rev. Immunol. 2009, 9:83-89.
20. Kendal A.R., Chen Y., Regateiro F.S., Ma J., Adams E., Cobbold S.P., Hori S., Waldmann H. Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance. J. Exp. Med. 2011, 208:2043-2053.
21. Khattri R., Cox T., Yasayko S.A., Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 2003, 4:337-342.
22. Kim H.P., Leonard W.J. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J. Exp. Med. 2007, 204:1543-1551.
23. Klein L., Jovanovic K. Regulatory T cell lineage commitment in the thymus. Semin. Immunol. 2011, 23:401-409.
24. Komatsu N., Mariotti-Ferrandiz M.E., Wang Y., Malissen B., Waldmann H., Hori S. Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc. Natl. Acad. Sci. USA 2009, 106:1903-1908.
25. Kretschmer K., Apostolou I., Hawiger D., Khazaie K., Nussenzweig M.C., von Boehmer H. Inducing and expanding regulatory T cell populations by foreign antigen. Nat. Immunol. 2005, 6:1219-1227.
26. Lathrop S.K., Santacruz N.A., Pham D., Luo J., Hsieh C.S. Antigen-specific peripheral shaping of the natural regulatory T cell population. J. Exp. Med. 2008, 205:3105-3117.
27. Le Campion A., Bourgeois C., Lambolez F., Martin B., Léaument S., Dautigny N., Tanchot C., Pénit C., Lucas B. Naive T cells proliferate strongly in neonatal mice in response to self-peptide/self-MHC complexes. Proc. Natl. Acad. Sci. USA 2002, 99:4538-4543.
28. Lio C.W., Hsieh C.S. Becoming self-aware: the thymic education of regulatory T cells. Curr. Opin. Immunol. 2011, 23:213-219.
29. Luche H., Weber O., Nageswara Rao T., Blum C., Fehling H.J. Faithful activation of an extra-bright red fluorescent protein in " knock-in" Cre-reporter mice ideally suited for lineage tracing studies. Eur. J. Immunol. 2007, 37:43-53.
30. Min B., McHugh R., Sempowski G.D., Mackall C., Foucras G., Paul W.E. Neonates support lymphopenia-induced proliferation. Immunity 2003, 18:131-140.
31. Murai M., Turovskaya O., Kim G., Madan R., Karp C.L., Cheroutre H., Kronenberg M. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat. Immunol. 2009, 10:1178-1184.
32. Polansky J.K., Kretschmer K., Freyer J., Floess S., Garbe A., Baron U., Olek S., Hamann A., von Boehmer H., Huehn J. DNA methylation controls Foxp3 gene expression. Eur. J. Immunol. 2008, 38:1654-1663.
33. Polansky J.K., Schreiber L., Thelemann C., Ludwig L., Krüger M., Baumgrass R., Cording S., Floess S., Hamann A., Huehn J. Methylation matters: binding of Ets-1 to the demethylated Foxp3 gene contributes to the stabilization of Foxp3 expression in regulatory T cells. J. Mol. Med. 2010, 88:1029-1040.
34. Rubtsov Y.P., Niec R.E., Josefowicz S., Li L., Darce J., Mathis D., Benoist C., Rudensky A.Y. Stability of the regulatory T cell lineage in vivo. Science 2010, 329:1667-1671.
35. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 2004, 22:531-562.
36. Sakaguchi S., Sakaguchi N., Asano M., Itoh M., Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995, 155:1151-1164.
37. Schallenberg S., Tsai P.Y., Riewaldt J., Kretschmer K. Identification of an immediate Foxp3(-) precursor to Foxp3(+) regulatory T cells in peripheral lymphoid organs of nonmanipulated mice. J. Exp. Med. 2010, 207:1393-1407.
38. Thornton A.M., Korty P.E., Tran D.Q., Wohlfert E.A., Murray P.E., Belkaid Y., Shevach E.M. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 2010, 184:3433-3441.
39. Tran D.Q., Ramsey H., Shevach E.M. Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype. Blood 2007, 110:2983-2990.
40. Tsuji M., Komatsu N., Kawamoto S., Suzuki K., Kanagawa O., Honjo T., Hori S., Fagarasan S. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 2009, 323:1488-1492.
41. Wang J., Ioan-Facsinay A., van der Voort E.I., Huizinga T.W., Toes R.E. Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur. J. Immunol. 2007, 37:129-138.
42. Williams L.M., Rudensky A.Y. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat. Immunol. 2007, 8:277-284.
43. Xu L., Kitani A., Fuss I., Strober W. Cutting edge: regulatory T cells induce CD4+CD25-Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta. J. Immunol. 2007, 178:6725-6729.
44. Yang X.O., Nurieva R., Martinez G.J., Kang H.S., Chung Y., Pappu B.P., Shah B., Chang S.H., Schluns K.S., Watowich S.S., et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 2008, 29:44-56.
45. Zheng Y., Josefowicz S., Chaudhry A., Peng X.P., Forbush K., Rudensky A.Y. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 2010, 463:808-812.
46. Zhou X., Bailey-Bucktrout S.L., Jeker L.T., Penaranda C., Martínez-Llordella M., Ashby M., Nakayama M., Rosenthal W., Bluestone J.A. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. 2009, 10:1000-1007.
47. Ziegler S.F. FOXP3: of mice and men. Annu. Rev. Immunol. 2006, 24:209-226.
48. Zorn E., Nelson E.A., Mohseni M., Porcheray F., Kim H., Litsa D., Bellucci R., Raderschall E., Canning C., Soiffer R.J., 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, 108:1571-1579.