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

Volumn 108, Issue 5, 2006, Pages 1571-1579

  Zorn, Emmanuel ^a   Nelson, Erik A ^a   Mohseni, Mehrdad ^a   Porcheray, Fabrice ^a   Kim, Haesook ^a   Litsa, Despina ^a   Bellucci, Roberto ^a   Raderschall, Elke ^a   Canning, Christine ^a   Soiffer, Robert J ^a   Frank, David A ^a   Ritz, Jerome ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; RECOMBINANT INTERLEUKIN 2; STAT PROTEIN; STAT3 PROTEIN; STAT5 PROTEIN; TRANSCRIPTION FACTOR FOXP3;

ADULT; AGED; ARTICLE; BINDING SITE; CANCER; CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL TRANSPORT; CHRONIC MYELOID LEUKEMIA; CLINICAL ARTICLE; CONTROLLED STUDY; HUMAN; HUMAN CELL; INTRON; LOW DRUG DOSE; NATURAL KILLER CELL; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION;

EID: 33747801470     PISSN: 00064971     EISSN: 00064971     Source Type: Journal    
DOI: 10.1182/blood-2006-02-004747     Document Type: Article

References (53)

1. Malek TR, Bayer AL. Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol. 2004;4:665-674.
2. Nelson BH. IL-2, regulatory T cells, and tolerance. J Immunol. 2004;172:3983-3988.
3. Sadlack B, Merz H, Schorle H, Schimpl A, Feller AC, Horak I. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell. 1993;75:253-261.
4. Willerford DM, Chen J, Ferry JA, Davidson L, Ma A, Alt FW. Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment. Immunity. 1995;3:521-530.
5. Bayer AL, Yu A, Adeegbe D, Malek TR. Essential role for interleukin-2 for CD4(+)CD25(+) T regulatory cell development during the neonatal period. J Exp Med. 2005;201:769-777.
6. Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol. 2005;6:1142-1151.
7. Knoechel B, Lohr J, Kahn E, Bluestone JA, Abbas AK. Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen. J Exp Med. 2005;202:1375-1386.
8. Setoguchi R, Hori S, Takahashi T, Sakaguchi S. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med. 2005;201:723-735.
9. Ahmadzadeh M, Rosenberg SA. IL-2 administration increases CD4+CD25hiFoxp3+ regulatory T cells in cancer patients. Blood. Prepublished on November 22, 2005, as DOI 10.1182/blood-2005-06-2399.
10. (Now available as Blood. 2006;107:2409-2414.)
11. Sereti I, Imamichi H, Natarajan V, et al. In vivo expansion of CD4CD45RO-CD25 T cells expressing foxP3 in IL-2-treated HIV-infected patients. J Clin Invest. 2005;115:1839-1847.
12. Zhang H, Chua KS, Guimond M, et al. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med. 2005;11:1238-1243.
13. Cesana GC, DeRaffele G, Cohen S, et al. Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J Clin Oncol. 2006;24:1169-1177.
14. Frank DA, Robertson MJ, Bonni A, Ritz J, Greenberg ME. Interleukin 2 signaling involves the phosphorylation of Stat proteins. Proc Natl Acad Sci U S A. 1995;92:7779-7783.
15. Antov A, Yang L, Vig M, Baltimore D, Van Parijs L. Essential role for STAT5 signaling in CD25+CD4+ regulatory T cell homeostasis and the maintenance of self-tolerance. J Immunol. 2003;171:3435-3441.
16. Bensinger SJ, Walsh PT, Zhang J, et al. Distinct IL-2 receptor signaling pattern in CD4+CD25+ regulatory T cells. J Immunol. 2004;172:5287-5296.
17. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4:330-336.
18. Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity. 2005;22:329-341.
19. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057-1061.
20. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001;27:20-21.
21. Brunkow ME, Jeffery EW, Hjerrild KA, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet. 2001;27:68-73.
22. Wildin RS, Ramsdell F, Peake J, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001;27:18-20.
23. Soiffer RJ, Murray C, Cochran K, et al. Clinical and immunologic effects of prolonged infusion of low-dose recombinant interleukin-2 after autologous and T-cell-depleted allogeneic bone marrow transplantation. Blood. 1992;79:517-526.
24. Soiffer RJ, Murray C, Gonin R, Ritz J. Effect of low-dose interleukin-2 on disease relapse after T-cell-depleted allogeneic bone marrow transplantation. Blood. 1994;84:964-971.
25. Imada K, Leonard WJ. The Jak-STAT pathway. Mol Immunol. 2000;37:1-11.
26. Onishi M, Nosaka T, Misawa K, et al. Identification and characterization of a constitutively active STAT5 mutant that promotes cell proliferation. Mol Cell Biol. 1998;18:3871-3879.
27. Bromberg JF, Wrzeszczynska MH, Devgan G, et al. Stat3 as an oncogene. Cell. 1999;98:295-303.
28. Caligiuri MA, Murray C, Soiffer RJ, et al. Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity. J Clin Oncol. 1991;9:2110-2119.
29. de la Rosa M, Rutz S, Dorninger H, Scheffold A. Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. Eur J Immunol. 2004;34:2480-2488.
30. Thornton AM, Donovan EE, Piccirillo CA, Shevach EM. Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function. J Immunol. 2004;172:6519-6523.
31. Nelson EA, Walker SR, Alvarez JV, Frank DA. Isolation of unique STAT5 targets by chromatin immunoprecipitation-based gene identification. J Biol Chem. 2004;279:54724-54730.
32. Snow JW, Abraham N, Ma MC, Herndier BG, Pastuszak AW, Goldsmith MA. Loss of tolerance and autoimmunity affecting multiple organs in STAT5A/5B-deficient mice. J Immunol. 2003;171:5042-5050.
33. Malek TR, Yu A, Vincek V, Scibelli P, Kong L. CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice: implications for the nonredundant function of IL-2. Immunity. 2002;17:167-178.
34. Kortylewski M, Kujawski M, Wang T, et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med. 2005;11:1314-1321.
35. Watanabe N, Wang YH, Lee HK, et al. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature. 2005;436:1181-1185.
36. Caligiuri MA, Murray C, Robertson MJ, et al. Selective modulation of human natural killer cells in vivo after prolonged infusion of low dose recombinant interleukin 2. J Clin Invest. 1993;91:123-132.
37. Caligiuri MA, Zmuidzinas A, Manley TJ, Levine H, Smith KA, Ritz J. Functional consequences of interleukin 2 receptor expression on resting human lymphocytes: identification of a novel natural killer cell subset with high affinity receptors. J Exp Med. 1990;171:1509-1526.
38. Yu CR, Young HA, Ortaldo JR. Characterization of cytokine differential induction of STAT complexes in primary human T and NK cells. J Leukoc Biol. 1998;64:245-258.
39. Wang KS, Frank DA, Ritz J. Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4. Blood. 2000;95:3183-3190.
40. Smith KA. Interleukin-2: inception, impact, and implications. Science. 1988;240:1169-1176.
41. Soiffer RJ, Murray C, Shapiro C, et al. Expansion and manipulation of natural killer cells in patients with metastatic cancer by low-dose continuous infusion and intermittent bolus administration of interleukin 2. Clin Cancer Res. 1996;2:493-499.
42. Andersen MH, Gehl J, Reker S, et al. Dynamic changes of specific T cell responses to melanoma correlate with IL-2 administration. Semin Cancer Biol. 2003;13:449-459.
43. Slingluff CL Jr, Petroni GR, Yamshchikov GV, et al. Immunologic and clinical outcomes of vaccination with a multiepitope melanoma peptide vaccine plus low-dose interleukin-2 administered either concurrently or on a delayed schedule. J Clin Oncol. 2004;22:4474-4485.
44. Escobar A, Lopez M, Serrano A, et al. Dendritic cell immunizations alone or combined with low doses of interleukin-2 induce specific immune responses in melanoma patients. Clin Exp Immunol. 2005;142:555-568.
45. Hori S, Takahashi T, Sakaguchi S. Control of autoimmunity by naturally arising regulatory CD4+ T cells. Adv Immunol. 2003;81:331-371.
46. Zorn E, Kim HT, Lee SJ, et al. Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood. 2005;106:2903-2911.
47. Edinger M, Hoffmann P, Ermann J, et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9:1144-1150.
48. Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S. Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med. 2002;196:389-399.
49. Taylor PA, Lees CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood. 2002;99:3493-3499.
50. Trenado A, Charlotte F, Fisson S, et al. Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia. J Clin Invest. 2003;112:1688-1696.
51. Sykes M, Romick ML, Hoyles KA, Sachs DH. In vivo administration of interleukin 2 plus T cell-depleted syngeneic marrow prevents graft-versus-host disease mortality and permits alloengraftment. J Exp Med. 1990;171:645-658.
52. Sykes M, Romick ML, Sachs DH. Interleukin 2 prevents graft-versus-host disease while preserving the graft-versus-leukemia effect of allogeneic T cells. Proc Natl Acad Sci U S A. 1990;87:5633-5637.
53. Roychowdhury S, Blaser BW, Freud AG, et al. IL-15 but not IL-2 rapidly induces lethal xenogeneic graft-versus-host disease. Blood. 2005;106:2433-2435.