In Vivo maintenance of human regulatory T cells during CD25 blockade

Journal of Immunology

Volumn 194, Issue 1, 2015, Pages 84-92

  Huss, David J ^a   Mehta, Devangi S ^a   Sharma, Akanksha ^a   You, Xiaojun ^a   Riester, Katherine A ^a   Sheridan, James P ^b   Amaravadi, Lakshmi S ^a   Elkins, Jacob S ^a   Fontenot, Jason D ^a  

^a BIOGEN   (United States)

^b ABBVIE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DACLIZUMAB; GAMMA INTERFERON; INTERLEUKIN 17; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 2 RECEPTOR BETA; INTERLEUKIN 2 RECEPTOR GAMMA; INTERLEUKIN 7 RECEPTOR; KI 67 ANTIGEN; PLACEBO; STAT5 PROTEIN; TRANSCRIPTION FACTOR FOXP3; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, HUMAN; IL2 PROTEIN, HUMAN; IL2RA PROTEIN, HUMAN; IL2RB PROTEIN, HUMAN; IL2RG PROTEIN, HUMAN; IMMUNOGLOBULIN G; IMMUNOSUPPRESSIVE AGENT; MONOCLONAL ANTIBODY;

ARTICLE; CELL CYCLE; CELL LINEAGE; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; HOMEOSTASIS; HUMAN; HUMAN CELL; IMMUNOPHENOTYPING; IN VIVO STUDY; LYMPHOCYTE COUNT; MULTIPLE SCLEROSIS; PHASE 2 CLINICAL TRIAL; PROMOTER REGION; PROTEIN ANALYSIS; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RASH; REGULATORY T LYMPHOCYTE; TREATMENT DURATION; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; BLOOD; CD4 LYMPHOCYTE COUNT; CLINICAL TRIAL; DRUG EFFECTS; GENETICS; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; METABOLISM; MULTIPLE SCLEROSIS, RELAPSING-REMITTING; PHOSPHORYLATION; RANDOMIZED CONTROLLED TRIAL;

ANTIBODIES, MONOCLONAL, HUMANIZED; CD4 LYMPHOCYTE COUNT; CELL CYCLE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; IMMUNOGLOBULIN G; IMMUNOSUPPRESSIVE AGENTS; INTERFERON-GAMMA; INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT; INTERLEUKIN-17; INTERLEUKIN-2; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; INTERLEUKIN-2 RECEPTOR BETA SUBUNIT; MULTIPLE SCLEROSIS, RELAPSING-REMITTING; PHOSPHORYLATION; PROMOTER REGIONS, GENETIC; SELF TOLERANCE; STAT5 TRANSCRIPTION FACTOR; T-LYMPHOCYTES, REGULATORY;

EID: 84919628870     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1402140     Document Type: Article

References (50)

1. Josefowicz, S. Z., L.-F. Lu, and A. Y. Rudensky. 2012. Regulatory T cells: Mechanisms of differentiation and function. Annu. Rev. Immunol. 30: 531-564.
2. Cheng, G., A. Yu, and T. R. Malek. 2011. T-cell tolerance and the multi-functional role of IL-2R signaling in T-regulatory cells. Immunol. Rev. 241: 63-76.
3. Wildin, R. S., F. Ramsdell, J. Peake, F. Faravelli, J. L. Casanova, N. Buist, E. Levy-Lahad, M. Mazzella, O. Goulet, L. Perroni, et al. 2001. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 27: 18-20.
4. Bacchetta, R., L. Passerini, E. Gambineri, M. Dai, S. E. Allan, L. Perroni, F. Dagna-Bricarelli, C. Sartirana, S. Matthes-Martin, A. Lawitschka, et al. 2006. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J. Clin. Invest. 116: 1713-1722.
5. Fontenot, J. D., M. A. Gavin, and A. Y. Rudensky. 2003. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4: 330-336.
6. Hori, S., T. Nomura, and S. Sakaguchi. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061.
7. Miyao, T., S. Floess, R. Setoguchi, H. Luche, H. J. Fehling, H. Waldmann, J. Huehn, and S. Hori. 2012. Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. Immunity 36: 262-275.
8. Brusko, T. M., A. L. Putnam, and J. A. Bluestone. 2008. Human regulatory T cells: Role in autoimmune disease and therapeutic opportunities. Immunol. Rev. 223: 371-390.
9. Zhou, X., S. L. Bailey-Bucktrout, L. T. Jeker, C. Penaranda, M. Martínez- Llordella, M. Ashby, M. Nakayama, W. Rosenthal, and J. A. Bluestone. 2009. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. 10: 1000-1007.
10. McClymont, S. A., A. L. Putnam, M. R. Lee, J. H. Esensten, W. Liu, M. A. Hulme, U. Hoffmuller, 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.
11. Bailey-Bucktrout, S. L., M. Martinez-Llordella, X. Zhou, B. Anthony, W. Rosenthal, H. Luche, H. J. Fehling, and J. A. Bluestone. 2013. Self-Antigendriven activation induces instability of regulatory T cells during an inflammatory autoimmune response. Immunity 39: 949-962.
12. Malek, T. R. 2008. The biology of interleukin-2. Annu. Rev. Immunol. 26: 453-479.
13. Malek, T. R., and I. Castro. 2010. Interleukin-2 receptor signaling: At the interface between tolerance and immunity. Immunity 33: 153-165.
14. Waldmann, T. A. 2002. The IL-2/IL-15 receptor systems: Targets for immunotherapy. J. Clin. Immunol. 22: 51-56.
15. Ota, K., M. Matsui, E. L. Milford, G. A. Mackin, H. L. Weiner, and D. A. Hafler. 1990. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346: 183-187.
16. Wucherpfennig, K. W., K. Ota, N. Endo, J. G. Seidman, A. Rosenzweig, H. L. Weiner, and D. A. Hafler. 1990. Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein. Science 248: 1016-1019.
17. Allegretta, M., J. A. Nicklas, S. Sriram, and R. J. Albertini. 1990. T cells responsive to myelin basic protein in patients with multiple sclerosis. Science 247: 718-721.
18. Gold, R., G. Giovannoni, K. Selmaj, E. Havrdova, X. Montalban, E. W. Radue, D. Stefoski, R. Robinson, K. Riester, J. Rana, et al; SELECT study investigators. 2013. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): A randomised, double-blind, placebo-controlled trial. Lancet 381: 2167-2175.
19. Wiendl, H., and C. C. Gross. 2013. Modulation of IL-2Ra with daclizumab for treatment of multiple sclerosis. Nat. Rev. Neurol. 9: 394-404.
20. Bielekova, B., M. Catalfamo, S. Reichert-Scrivner, A. Packer, M. Cerna, T. A. Waldmann, H. McFarland, P. A. Henkart, and R. Martin. 2006. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL- 2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc. Natl. Acad. Sci. USA 103: 5941-5946.
21. Martin, J. F., J. S. Perry, N. R. Jakhete, X. Wang, and B. Bielekova. 2010. An IL- 2 paradox: Blocking CD25 on T cells induces IL-2-driven activation of CD56 (bright) NK cells. J. Immunol. 185: 1311-1320.
22. Perry, J. S., S. Han, Q. Xu, M. L. Herman, L. B. Kennedy, G. Csako, and B. Bielekova. 2012. Inhibition of LTi cell development by CD25 blockade is associated with decreased intrathecal inflammation in multiple sclerosis. Sci. Transl. Med. 4: 145ra106.
23. Oh, U., G. Blevins, C. Griffith, N. Richert, D. Maric, C. R. Lee, H. McFarland, and S. Jacobson. 2009. Regulatory T cells are reduced during anti-CD25 antibody treatment of multiple sclerosis. Arch. Neurol. 66: 471-479.
24. Rech, A. J., R. Mick, S. Martin, A. Recio, N. A. Aqui, D. J. Powell, Jr., T. A. Colligon, J. A. Trosko, L. I. Leinbach, C. H. Pletcher, C. K. Tweed, A. DeMichele, K. R. Fox, S. M. Domchek, J. L. Riley, and R. H. Vonderheide. 2012. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients. Sci. Transl. Med. 4: 134ra62.
25. Sehouli, J., C. Loddenkemper, T. Cornu, T. Schwachula, U. Hoffmuller, A. Grutzkau, P. Lohneis, T. Dickhaus, J. Gröne, M. Kruschewski, et al. 2011. Epigenetic quantification of tumor-infiltrating T-lymphocytes. Epigenetics 6: 236-246.
26. Niemeyer, C. M., M. Adler, and R. Wacker. 2007. Detecting antigens by quantitative immuno-PCR. Nat. Protoc. 2: 1918-1930.
27. 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.
28. Sakaguchi, S., D. A. Vignali, A. Y. Rudensky, R. E. Niec, and H. Waldmann. 2013. The plasticity and stability of regulatory T cells. Nat. Rev. Immunol. 13: 461-467.
29. da Silva Martins, M., and C. A. Piccirillo. 2012. Functional stability of Foxp3+ regulatory T cells. Trends Mol. Med. 18: 454-462.
30. Bailey-Bucktrout, S. L., and J. A. Bluestone. 2011. Regulatory T cells: Stability revisited. Trends Immunol. 32: 301-306.
31. Baron, U., S. Floess, G. Wieczorek, K. Baumann, A. Grutzkau, 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.
32. 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.
33. Wieczorek, G., A. Asemissen, F. Model, I. Turbachova, S. Floess, V. Liebenberg, U. Baron, D. Stauch, K. Kotsch, J. Pratschke, et al. 2009. Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue. Cancer Res. 69: 599-608.
34. Yao, Z., Y. Kanno, M. Kerenyi, G. Stephens, L. Durant, W. T. Watford, A. Laurence, G. W. Robinson, E. M. Shevach, R. Moriggl, et al. 2007. Nonredundant roles for Stat5a/b in directly regulating Foxp3. Blood 109: 4368-4375.
35. Zorn, E., E. A. Nelson, M. Mohseni, F. Porcheray, H. Kim, D. Litsa, R. Bellucci, E. Raderschall, C. Canning, R. J. Soiffer, et al. 2006. 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 108: 1571-1579.
36. Carbone, F., V. De Rosa, P. B. Carrieri, S. Montella, D. Bruzzese, A. Porcellini, C. Procaccini, A. La Cava, and G. Matarese. 2014. Regulatory T cell proliferative potential is impaired in human autoimmune disease. Nat. Med. 20: 69-74.
37. Viglietta, V., C. Baecher-Allan, H. L. Weiner, and D. A. Hafler. 2004. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med. 199: 971-979.
38. Haas, J., A. Hug, A. Viehöver, B. Fritzsching, C. S. Falk, A. Filser, T. Vetter, L. Milkova, M. Korporal, B. Fritz, et al. 2005. Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur. J. Immunol. 35: 3343-3352.
39. Kumar, M., N. Putzki, V. Limmroth, R. Remus, M. Lindemann, D. Knop, N. Mueller, C. Hardt, E. Kreuzfelder, and H. Grosse-Wilde. 2006. CD4+CD25+ FoxP3+ T lymphocytes fail to suppress myelin basic protein-induced proliferation in patients with multiple sclerosis. J. Neuroimmunol. 180: 178-184.
40. Schneider, A., S. A. Long, K. Cerosaletti, C. T. Ni, P. Samuels, M. Kita, and J. H. Buckner. 2013. In active relapsing-remitting multiple sclerosis, effector T cell resistance to adaptive Tregs involves IL-6-mediated signaling. Sci. Transl. Med. 5: 170ra15.
41. Kinnunen, T., N. Chamberlain, H. Morbach, T. Cantaert, M. Lynch, P. Preston- Hurlburt, K. C. Herold, D. A. Hafler, K. C. O'Connor, and E. Meffre. 2013. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. J. Clin. Invest. 123: 2737-2741.
42. Venken, K., N. Hellings, R. Liblau, and P. Stinissen. 2010. Disturbed regulatory T cell homeostasis in multiple sclerosis. Trends Mol. Med. 16: 58-68.
43. Costantino, C. M., C. Baecher-Allan, and D. A. Hafler. 2008. Multiple sclerosis and regulatory T cells. J. Clin. Immunol. 28: 697-706.
44. Oldenhove, G., N. Bouladoux, E. A. Wohlfert, J. A. Hall, D. Chou, L. Dos Santos, S. O'Brien, R. Blank, E. Lamb, S. Natarajan, et al. 2009. Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity 31: 772-786.
45. Rubtsov, Y. P., R. E. Niec, S. Josefowicz, L. Li, J. Darce, D. Mathis, C. Benoist, and A. Y. Rudensky. 2010. Stability of the regulatory T cell lineage in vivo. Science 329: 1667-1671.
46. Komatsu, N., K. Okamoto, S. Sawa, T. Nakashima, M. Oh-hora, T. Kodama, S. Tanaka, J. A. Bluestone, and H. Takayanagi. 2014. Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. Nat. Med. 20: 62-68.
47. Zhang, Y., M. McClellan, L. Efros, D. Shi, B. Bielekova, M. T. Tang, V. Vexler, and J. P. Sheridan. 2014. Daclizumab reduces CD25 levels on T cells through monocyte-mediated trogocytosis. Mult. Scler. 20: 156-164.
48. Villarino, A. V., C. M. Tato, J. S. Stumhofer, Z. Yao, Y. K. Cui, L. Hennighausen, J. J. O'Shea, and C. A. Hunter. 2007. Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals. J. Exp. Med. 204: 65-71.
49. Jiang, W., N. R. Chai, D. Maric, and B. Bielekova. 2011. Unexpected role for granzyme K in CD56bright NK cell-mediated immunoregulation of multiple sclerosis. J. Immunol. 187: 781-790.
50. Li, Z., W. K. Lim, S. P. Mahesh, B. Liu, and R. B. Nussenblatt. 2005. Cutting edge: In vivo blockade of human IL-2 receptor induces expansion of CD56(bright) regulatory NK cells in patients with active uveitis. J. Immunol. 174: 5187-5191.