Helios+ and Helios- cells coexist within the natural Foxp3+ T regulatory cell subset in humans

Journal of Immunology

Volumn 190, Issue 5, 2013, Pages 2001-2008

  Himmel, Megan E ^a   MacDonald, Katherine G ^a   Garcia, Rosa V ^a   Steiner, Theodore S ^b   Levings, Megan K ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CD39 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR HELIOS; UNCLASSIFIED DRUG;

ANTIGEN EXPRESSION; ARTICLE; CELL CLONE; CELL ISOLATION; CELL LINEAGE; CELL POLARITY; CELL SURFACE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DEMETHYLATION; FOXP3+ REGULATORY T LYMPHOCYTE; HELIOS+ REGULATORY T LYMPHOCYTE; HELIOS+- REGULATORY T LYMPHOCYTE; HUMAN; HUMAN CELL; IMMUNOREGULATION; LYMPHOCYTE FUNCTION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TH1 CELL;

ANTIGENS, CD; APYRASE; CELL DIFFERENTIATION; CELL LINEAGE; CHEMOKINE CCL3; CLONE CELLS; CTLA-4 ANTIGEN; FLOW CYTOMETRY; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION; HUMANS; IKAROS TRANSCRIPTION FACTOR; IMMUNOPHENOTYPING; INTERFERON-GAMMA; ORGAN SPECIFICITY; T-LYMPHOCYTES, REGULATORY; THYMUS GLAND;

EID: 84874232301     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1201379     Document Type: Article

References (41)

1. Sakaguchi, S., F. Powrie, and R. M. Ransohoff. 2012. Re-establishing immunological self-tolerance in autoimmune disease. Nat. Med. 18: 54-58.
2. Shevach, E. M. 2011. Biological functions of regulatory T cells. Adv. Immunol. 112: 137-176.
3. Vignali, D. A., L. W. Collison, and C. J. Workman. 2008. How regulatory T cells work. Nat. Rev. Immunol. 8: 523-532.
4. Curotto de Lafaille, M. A., and J. J. Lafaille. 2009. Natural and adaptive Foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 30: 626-635.
5. Horwitz, D. A., S. G. Zheng, and J. D. Gray. 2008. Natural and TGF-b-induced Foxp3+CD4+CD25+ regulatory T cells are not mirror images of each other. Trends Immunol. 29: 429-435.
6. Miyara, M., Y. Yoshioka, A. Kitoh, T. Shima, K. Wing, A. Niwa, C. Parizot, C. Taflin, T. Heike, D. Valeyre, et al. 2009. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30: 899-911.
7. Valmori, D., C. Raffin, I. Raimbaud, and M. Ayyoub. 2010. Human RORgt+ TH17 cells preferentially differentiate from naive FOXP3+ Treg in the presence of lineage-specific polarizing factors. Proc. Natl. Acad. Sci. USA 107: 19402-19407.
8. Hsieh, C. S., H. M. Lee, and C. W. Lio. 2012. Selection of regulatory T cells in the thymus. Nat. Rev. Immunol. 12: 157-167.
9. Shevach, E. M. 2009. Mechanisms of Foxp3+ T regulatory cell-mediated suppression. Immunity 30: 636-645.
10. Lee, H. M., J. L. Bautista, and C. S. Hsieh. 2011. Thymic and peripheral differentiation of regulatory T cells. Adv. Immunol. 112: 25-71.
11. Thornton, A. M., P. E. Korty, D. Q. Tran, E. A. Wohlfert, P. E. Murray, Y. Belkaid, and E. M. Shevach. 2010. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184: 3433-3441.
12. Akimova, T., U. H. Beier, L. Wang, M. H. Levine, and W. W. Hancock. 2011. Helios expression is a marker of T cell activation and proliferation. PLoS ONE 6: e24226.
13. Verhagen, J., and D. C. Wraith. 2010. Comment on "Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells". J. Immunol. 185: 7129, author reply 7130.
14. Gottschalk, R. A., E. Corse, and J. P. Allison. 2012. Expression of Helios in peripherally induced Foxp3+ regulatory T cells. J. Immunol. 188: 976-980.
15. Levings, M. K., R. Sangregorio, C. Sartirana, A. L. Moschin, M. Battaglia, P. C. Orban, and M. G. Roncarolo. 2002. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells. J. Exp. Med. 196: 1335-1346.
16. Baecher-Allan, C. M., C. M. Costantino, G. L. Cvetanovich, C. W. Ashley, G. Beriou, M. Dominguez-Villar, and D. A. Hafler. 2011. CD2 costimulation reveals defective activity by human CD4+CD25hi regulatory cells in patients with multiple sclerosis. J. Immunol. 186: 3317-3326.
17. Broady, R., J. Yu, and M. K. Levings. 2009. ATG-induced expression of FOXP3 in human CD4+ T cells in vitro is associated with T-cell activation and not the induction of FOXP3+ T regulatory cells. Blood 114: 5003-5006.
18. Baron, U., S. Floess, G. Wieczorek, K. Baumann, A. Grützkau, J. Dong, A. Thiel, T. J. Boeld, P. Hoffmann, M. Edinger, et al. 2007. DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells. Eur. J. Immunol. 37: 2378-2389.
19. Reiss, D., Y. Zhang, and D. L. Mager. 2007. Widely variable endogenous retroviral methylation levels in human placenta. Nucleic Acids Res. 35: 4743-4754.
20. Cohen, C. J., S. Q. Crome, K. G. MacDonald, E. L. Dai, D. L. Mager, and M. K. Levings. 2011. Human Th1 and Th17 cells exhibit epigenetic stability at signature cytokine and transcription factor loci. J. Immunol. 187: 5615-5626.
21. Crellin, N. K., R. V. Garcia, and M. K. Levings. 2007. Altered activation of AKT is required for the suppressive function of human CD4+CD25+ T regulatory cells. Blood 109: 2014-2022.
22. Levings, M. K., R. Sangregorio, F. Galbiati, S. Squadrone, R. de Waal Malefyt, and M. G. Roncarolo. 2001. IFN-a and IL-10 induce the differentiation of human type 1 T regulatory cells. J. Immunol. 166: 5530-5539.
23. Kim, Y. C., R. Bhairavabhotla, J. Yoon, A. Golding, A. M. Thornton, D. Q. Tran, and E. M. Shevach. 2012. Oligodeoxynucleotides stabilize Helios-expressing Foxp3+ human T regulatory cells during in vitro expansion. Blood 119: 2810-2818.
24. Arlettaz, L., C. Barbey, F. Dumont-Girard, C. Helg, B. Chapuis, E. Roux, and E. Roosnek. 1999. CD45 isoform phenotypes of human T cells: CD4+CD45RA2 RO+ memory T cells re-acquire CD45RA without losing CD45RO. Eur. J. Immunol. 29: 3987-3994.
25. Sallusto, F., D. Lenig, R. Fö rster, M. Lipp, and A. Lanzavecchia. 1999. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401: 708-712.
26. Kimmig, S., G. K. Przybylski, C. A. Schmidt, K. Laurisch, B. Möwes, A. Radbruch, and A. Thiel. 2002. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med. 195: 789-794.
27. Allan, S. E., S. Q. Crome, N. K. Crellin, L. Passerini, T. S. Steiner, R. Bacchetta, M. G. Roncarolo, and M. K. Levings. 2007. Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int. Immunol. 19: 345-354.
28. Borsellino, G., M. Kleinewietfeld, D. Di Mitri, A. Sternjak, A. Diamantini, R. Giometto, S. Höpner, D. Centonze, G. Bernardi, M. L. Dell'Acqua, et al. 2007. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110: 1225-1232.
29. Levings, M. K., R. Sangregorio, and M. G. Roncarolo. 2001. Human Cd25+Cd4+ T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J. Exp. Med. 193: 1295-1302.
30. Getnet, D., J. F. Grosso, M. V. Goldberg, T. J. Harris, H. R. Yen, T. C. Bruno, N. M. Durham, E. L. Hipkiss, K. J. Pyle, S. Wada, et al. 2010. A role for the transcription factor Helios in human CD4+CD25+ regulatory T cells. Mol. Immunol. 47: 1595-1600.
31. Himmel, M. E., S. Q. Crome, S. Ivison, C. Piccirillo, T. S. Steiner, and M. K. Levings. 2010. Human CD4+FOXP3+ regulatory T cells produce CXCL8 and recruit neutrophils. Eur. J. Immunol. 41: 115-122.
32. Czystowska, M., L. Strauss, C. Bergmann, M. Szajnik, H. Rabinowich, and T. L. Whiteside. 2010. Reciprocal granzyme/perforin-mediated death of human regulatory and responder T cells is regulated by interleukin-2 (IL-2). J. Mol. Med. 88: 577-588.
33. Szabo, S. J., S. T. Kim, G. L. Costa, X. Zhang, C. G. Fathman, and L. H. Glimcher. 2000. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655-669.
34. Koch, M. A., G. Tucker-Heard, N. R. Perdue, J. R. Killebrew, K. B. Urdahl, and D. J. Campbell. 2009. The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat. Immunol. 10: 595-602.
35. Schmetterer, K. G., A. Neunkirchner, and W. F. Pickl. 2012. Naturally occurring regulatory T cells: markers, mechanisms, and manipulation. FASEB J. 26: 2253-2276.
36. Dominguez-Villar, M., C. M. Baecher-Allan, and D. A. Hafler. 2011. Identification of T helper type 1-like, Foxp3+ regulatory T cells in human autoimmune disease. Nat. Med. 17: 673-675.
37. Wood, K. J., and B. Sawitzki. 2006. Interferon gamma: a crucial role in the function of induced regulatory T cells in vivo. Trends Immunol. 27: 183-187.
38. McClymont, S. A., A. L. Putnam, M. R. Lee, J. H. Esensten,W. Liu, M. A. Hulme, U. Hoffmüller, U. Baron, S. Olek, J. A. Bluestone, and T. M. Brusko. 2011. Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes. J. Immunol. 186: 3918-3926.
39. Huehn, J., J. K. Polansky, and A. Hamann. 2009. Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nat. Rev. Immunol. 9: 83-89.
40. Polansky, J. K., K. Kretschmer, J. Freyer, S. Floess, A. Garbe, U. Baron, S. Olek, A. Hamann, H. von Boehmer, and J. Huehn. 2008. DNA methylation controls Foxp3 gene expression. Eur. J. Immunol. 38: 1654-1663.
41. Fu, W., A. Ergun, T. Lu, J. A. Hill, S. Haxhinasto, M. S. Fassett, R. Gazit, S. Adoro, L. Glimcher, S. Chan, et al. 2012. A multiply redundant genetic switch "locks in" the transcriptional signature of regulatory T cells. Nat. Immunol. 13: 972-980.