Sustained invivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells

Journal of Autoimmunity

Volumn 56, Issue , 2015, Pages 66-80

  Bell, Charles J M ^a   Sun, Yongliang ^b   Nowak, Urszula M ^b   Clark, Jan ^a   Howlett, Sarah ^a   Pekalski, Marcin L ^a   Yang, Xin ^a   Ast, Oliver ^d   Waldhauer, Inja ^c   Freimoser Grundschober, Anne ^d   Moessner, Ekkehard ^d   Umana, Pablo ^c   Klein, Christian ^c   Hosse, Ralf J ^d   Wicker, Linda S ^a   Peterson, Laurence B ^a,b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b HOFFMANN LA ROCHE INC   (United States)

^c Roche Pharmaceutical Research and Early Development Oncology Discovery and Translational Area Roche Innovation Center Zurich   (Switzerland)

^d Roche Pharmaceutical Research and Early Development   (Switzerland)

Author keywords

Autoimmunity; Cytokine therapy; Graft versus host disease; IL 2 fusion proteins; Regulatory T cells

Indexed keywords

ALDESLEUKIN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; HYBRID PROTEIN; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G1 INTERLEUKIN 2 FUSION PROTEIN; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; KI 67 ANTIGEN; STAT5A PROTEIN; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; FORKHEAD TRANSCRIPTION FACTOR; PROTEIN BINDING; RECOMBINANT PROTEIN; STAT5 PROTEIN;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CD4+ T LYMPHOCYTE; CELL EXPANSION; CONTROLLED STUDY; DOSE RESPONSE; DRUG MEGADOSE; EOSINOPHILIA; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LOW DRUG DOSE; MALE; MOUSE; NONHUMAN; NORMAL HUMAN; PLEIOTROPY; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; STOICHIOMETRY; T LYMPHOCYTE ACTIVATION; ANALOGS AND DERIVATIVES; ANIMAL; CHEMICALLY INDUCED; DEFICIENCY; DRUG EFFECTS; IMMUNOLOGY; KNOCKOUT MOUSE; LYMPHOCYTE COUNT; MACACA FASCICULARIS; METABOLISM; PHENOTYPE; PHOSPHORYLATION; T LYMPHOCYTE SUBPOPULATION;

ANIMALS; BIOMARKERS; CTLA-4 ANTIGEN; DOSE-RESPONSE RELATIONSHIP, DRUG; EOSINOPHILIA; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; INTERLEUKIN-2; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; LYMPHOCYTE COUNT; MACACA FASCICULARIS; MALE; MICE; MICE, KNOCKOUT; PHENOTYPE; PHOSPHORYLATION; PROTEIN BINDING; RECOMBINANT FUSION PROTEINS; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION; STAT5 TRANSCRIPTION FACTOR; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY;

EID: 84920116138     PISSN: 08968411     EISSN: 10959157     Source Type: Journal    
DOI: 10.1016/j.jaut.2014.10.002     Document Type: Article

References (47)

1. + regulatory T cells in the human immune system. Nat Rev Immunol 2010, 10:490-500.
2. Sakaguchi S., Wing K., Onishi Y., Prieto-Martin P., Yamaguchi T. Regulatory T cells: how do they suppress immune responses?. Int Immunol 2009, 21:1105-1111.
3. + regulatory T cells. Int Immunopharmacol 2011, 11:1489-1496.
4. Jeker L.T., Bour-Jordan H., Bluestone J.A. Breakdown in peripheral tolerance in type 1 diabetes in mice and humans. Cold Spring Harb Perspect Med 2012, 2:a007807.
5. Ramsdell F., Ziegler S.F. FOXP3 and scurfy: how it all began. Nat Rev Immunol 2014, 14:343-349.
6. Todd J.A. Etiology of type 1 diabetes. Immunity 2010, 32:457-467.
7. Hulme M.A., Wasserfall C.H., Atkinson M.A., Brusko T.M. Central role for interleukin-2 in type 1 diabetes. Diabetes 2012, 61:14-22.
8. O'Shea J.J., Holland S.M., Staudt L.M. JAKs and STATs in immunity, immunodeficiency, and cancer. NEngl J Med 2013, 368:161-170.
9. 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.
10. + Treg cells fit. Nat Immunol 2005, 6:1071-1072.
11. Nelson B.H. IL-2, regulatory T cells, and tolerance. JImmunol 2004, 172:3983-3988.
12. Yamanouchi J., Rainbow D., Serra P., Howlett S., Hunter K., Garner V.E., et al. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet 2007, 39:329-337.
13. Rand T.H., Silberstein D.S., Kornfeld H., Weller P.F. Human eosinophils express functional interleukin 2 receptors. JClin Investig 1991, 88:825-832.
14. Simon H.U., Plotz S., Simon D., Seitzer U., Braathen L.R., Menz G., et al. Interleukin-2 primes eosinophil degranulation in hypereosinophilia and Wells' syndrome. Eur J Immunol 2003, 33:834-839.
15. David D., Bani L., Moreau J.L., Demaison C., Sun K., Salvucci O., et al. Further analysis of interleukin-2 receptor subunit expression on the different human peripheral blood mononuclear cell subsets. Blood 1998, 91:165-172.
16. Pekalski M.L., Ferreira R.C., Coulson R.M., Cutler A.J., Guo H., Smyth D.J., et al. Postthymic expansion in human CD4 naive T cells defined by expression of functional high-affinity IL-2 receptors. JImmunol 2013, 190:2554-2566.
17. + regulatory T cell function. JImmunol 2012, 188:4644-4653.
18. high T cells in type 1 diabetes may be partially mediated by IL-2 deprivation. PLoS One 2009, 4:e6527.
19. Malek T.R., Bayer A.L. Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol 2004, 4:665-674.
20. Koreth J., Matsuoka K., Kim H.T., McDonough S.M., Bindra B., Alyea E.P., et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. NEngl J Med 2011, 365:2055-2066.
21. Saadoun D., Rosenzwajg M., Joly F., Six A., Carrat F., Thibault V., et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. NEngl J Med 2011, 365:2067-2077.
22. Kennedy-Nasser A.A., Ku S., Castillo-Caro P., Hazrat Y., Wu M.F., Liu H., et al. Ultra low-dose IL-2 for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation mediates expansion of regulatory t cells without diminishing antiviral and antileukemic activity. Clin Cancer Res 2014, 20:2215-2225.
23. Ito S., Bollard C.M., Carlsten M., Melenhorst J.J., Biancotto A., Wang E., et al. Ultra-low dose interleukin-2 promotes immune-modulating function of regulatory t cells and natural killer cells in healthy volunteers. Mol Ther 2014, 7:1388-1395.
24. Hartemann A., Bensimon G., Payan C.A., Jacqueminet S., Bourron O., Nicolas N., et al. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2013, 1:295-305.
25. Waldron-Lynch F., Kareclas P., Irons K., Walker N.M., Mander A., Wicker L.S., et al. Rationale and study design of the adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D): a non-randomised, open label, adaptive dose finding trial. BMJ Open 2014, 4:e005559.
26. Konrad M.W., Hemstreet G., Hersh E.M., Mansell P.W., Mertelsmann R., Kolitz J.E., et al. Pharmacokinetics of recombinant interleukin 2 in humans. Cancer Res 1990, 50:2009-2017.
27. Vazquez-Lombardi R., Roome B., Christ D. Molecular engineering of therapeutic cytokines. Antibodies 2013, 2:426-451.
28. Carter P. Bispecific human IgG by design. JImmunol Methods 2001, 248:7-15.
29. Ridgway J.B., Presta L.G., Carter P. 'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng 1996, 9:617-621.
30. Piscitelli S.C., Wells M.J., Metcalf J.A., Baseler M., Stevens R., Davey R.T. Pharmacokinetics and pharmacodynamics of subcutaneous interleukin-2 in HIV-infected patients. Pharmacotherapy 1996, 16:754-759.
31. Hinton P.R., Xiong J.M., Johlfs M.G., Tang M.T., Keller S., Tsurushita N. An engineered human IgG1 antibody with longer serum half-life. JImmunol 2006, 176:346-356.
32. Willerford D.M., Chen J., Ferry J.A., Davidson L., Ma A., Alt F.W. Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment. Immunity 1995, 3:521-530.
33. Wuest S.C., Edwan J.H., Martin J.F., Han S., Perry J.S., Cartagena C.M., et al. Arole for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy. Nat Med 2011, 17:604-609.
34. Krieg C., Letourneau S., Pantaleo G., Boyman O. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci U S A 2010, 107:11906-11911.
35. Long S.A., Rieck M., Sanda S., Bollyky J.B., Samuels P.L., Goland R., et al. Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs beta-cell function. Diabetes 2012, 61:2340-2348.
36. 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.
37. Ohkura N., Kitagawa Y., Sakaguchi S. Development and maintenance of regulatory T cells. Immunity 2013, 38:414-423.
38. + conventional T cells. Eur J Immunol 2007, 37:2378-2389.
39. Ohkura N., Hamaguchi M., Morikawa H., Sugimura K., Tanaka A., Ito Y., et al. Tcell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity 2012, 37:785-799.
40. + T cells expressing the FoxP3 transcription factor. Immunity 2009, 30:899-911.
41. Long S.A., Buckner J.H., Greenbaum C.J. IL-2 therapy in type 1 diabetes: "trials" and tribulations. Clin Immunol 2013, 149:324-331.
42. Reagan-Shaw S., Nihal M., Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008, 22:659-661.
43. + regulatory T cells in nonhuman primates. Am J Transpl 2012, 12:2532-2537.
44. + T regulatory and T effector cells and confers resistance to severe tuberculosis (TB): implicative Treg-T effector cooperation in immunity to TB. JImmunol 2012, 188:4278-4288.
45. Levine A.G., Arvey A., Jin W., Rudensky A.Y. Continuous requirement for the TCR in regulatory T cell function. Nat Immunol 2014, Sep 28, [Epub ahead of print]. 10.1038/ni.3004.
46. Piscitelli S.C., Forrest A., Vogel S., Chaitt D., Metcalf J., Stevens R., et al. Pharmacokinetic modeling of recombinant interleukin-2 in patients with human immunodeficiency virus infection. Clin Pharmacol Ther 1998, 64:492-498.
47. Yamada Y., Aoyama A., Tocco G., Boskovic S., Nadazdin O., Alessandrini A., et al. Differential effects of denileukin diftitox IL-2 immunotoxin on NK and regulatory T cells in nonhuman primates. JImmunol 2012, 188:6063-6070.