Targeting of IL-2 receptor with a caspase fusion protein disrupts autoimmunity in prediabetic and diabetic NOD mice

Diabetologia

Volumn 53, Issue 2, 2010, Pages 356-368

  Yarkoni, S ^a   Kaminitz, A ^b   Sagiv, Y ^a   Askenasy, N ^b,c  

^a GASR Biotechnology   (Israel)

^b SCHNEIDER CHILDREN S MEDICAL CENTER OF ISRAEL   (Israel)

^c CEDARS SINAI MEDICAL CENTER   (United States)

Author keywords

Apoptosis; Cyclophosphamide; IL 2 fusion proteins; Insulitis; NOD; T regulatory cells

Indexed keywords

CASPASE 3; CD4 ANTIGEN; CYCLOPHOSPHAMIDE; HYBRID PROTEIN; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 2 RECEPTOR ALPHA; TRANSCRIPTION FACTOR FOXP3;

ADOPTIVE TRANSFER; ALPHA CHAIN; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CELL SURVIVAL; CONTROLLED STUDY; DIABETES MELLITUS; HYPERGLYCEMIA; IN VITRO STUDY; INFLAMMATION; INSULITIS; LYMPH NODE; MOUSE; NONHUMAN; NONOBESE DIABETIC MOUSE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION; SCID MOUSE; T LYMPHOCYTE; THYMUS; WILD TYPE;

ANIMALS; CASPASE 3; CD4-POSITIVE T-LYMPHOCYTES; CELL DIVISION; DIABETES MELLITUS, TYPE 1; INTERLEUKIN-2; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; LYMPH NODES; MICE; MICE, INBRED NOD; PANCREAS; PREDIABETIC STATE; RECEPTORS, INTERLEUKIN-2; RECOMBINANT FUSION PROTEINS; SPLEEN; T-LYMPHOCYTES;

EID: 77949276812     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-009-1604-4     Document Type: Article

References (56)

1. Delovitch TL, Singh B (1997) The non-obese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity 7:727-738
2. Kishimoto H, Sprent J (2001) A defect in central tolerance in NOD mice. Nat Immunol 2:1025-1031
3. Anderson MS, Bluestone JA (2004) The NOD mouse. A model of immune dysregulation. Annu Rev Immunol 20:447-485
4. Brode S, Raine T, Zaccone P, Cooke A (2006) Cyclophosphamide-induced type-1 diabetes in the NOD mouse is associated with a reduction of CD4+CD25+Foxp3+ regulatory T cells. J Immunol 177:6603-6612
5. Lutsiak ME, Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H (2005) Inhibition of CD4+25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 105:2862-2868
6. Hadaya K, Kared H, Masson A, Chatenoud L, Zavala F (2005) GCSF treatment prevents cyclophosphamide acceleration of autoimmune diabetes in the NOD mouse. J Autoimmun 24:125-134
7. Chatenoud L, Primo J, Bach JF (1997) CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol 158:2947-2954
8. Chatenoud L, Bluestone JA (2007) CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol 7:622-632
9. Fehervari Z, Yamaguchi T, Sakaguchi S (2006) The dichotomous role of IL-2: tolerance vs immunity. Trends Immunol 27:109-111
10. Yarkoni S, Kaminitz A, Sagiv Y, Yaniv I, Askenasy N (2008) Involvement of IL-2 in homeostasis of regulatory T cells: the IL-2 cycle. BioEssays 30:875-888
11. Suri-Payer E, Amar AZ, Thornton AM, Shevach EM (1998) CD4+ CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. J Immunol 160:1212-1218
12. Kuniyasu Y, Takahashi T, Itoh M, Shimizu J, Toda G, Sakaguchi S (2000) Naturally anergic and suppressive CD25+CD4+ T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation. Int Immunol 12:1145-1155
13. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155:1151-1164
14. Malek TR, Bayer AL (2004) Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol 4:665-674
15. Nelson BH (2004) IL-2, regulatory T cells, and tolerance. J Immunol 172:3983-3988
16. Setoguchi R, Hori S, Takahashi T, Sakaguchi S (2005) 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 201:723-735
17. Serreze DV, Hamaguchi K, Leiter EH (1989) Immunostimulation circumvents diabetes in NOD/Lt mice. J Autoimmun 2:759-776
18. Tang Q, Adams JY, Penaranda C et al (2008) Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity 28:687-697
19. Zheng XX, Steele AW, Hancock WW et al (1999) IL-2 receptortargeted cytolytic IL-2/Fc fusion protein treatment blocks diabetogenic autoimmunity in nonobese diabetic mice. J Immunol 163:4041-4048
20. Pacheco-Solva A, Bastos MG, Pankewycz O, Nichols J, Murphy JR, Strom TB, Rubin-Kelley VE (1992) IL-2 toxin treatment blocks diabetogenic autoimmunity in NOD mice. Eur J Immunol 22:697-702
21. Woodworth TG (1993) Early clinical studies of IL-2 fusion toxin in patients with severe rheumatoid arthritis and recently onset insulindependent diabetes mellitus. Clin Exp Rheumatol 8:S177-S180
22. Sagiv Y, Kaminitz A, Lorberboum-Galski H, Askenasy N, Yarkoni S (2009) IL-2 targeted therapy in inflammatory bowel disease. Ann NY Acad Sci 1173:791-797
23. Yarkoni S, Sagiv Y, Kaminitz A, Askenasy N (2009) Targeted therapy to IL-2 receptor using diphtheria toxin and caspase-3 fusion proteins modulates regulatory T cells and ameliorates inflammatory colitis. Eur J Immunol 39:2850-2864
24. King C, Ilic A, Koelsch K, Sarvetnick N (2004) Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell 117:265-277
25. Shteingart S, Rapoport M, Grodzovski I, Sabag O, Lichtenstein M, Eavri R, Lorberboum-Galski H (2009) Therapeutic potency of IL2-caspase3 targeted treatment in a murine experimental model of inflammatory bowel disease (IBD). Gut 58:790-798
26. Franke DD, Yolcu ES, Alard P, Kosiewicz MM, Shirwan H (2007) A novel multimeric form of FasL modulates the ability of diabetogenic T cells to mediate type 1 diabetes in an adoptive transfer model. Mol Immunol 44:2884-2892
27. Ly D, Mi QS, Hussain S, Delovitch TL (2006) Protection from type 1 diabetes by invariant NK T cells requires the activity of CD4+CD25+ regulatory T cells. J Immunol 177:3695-3704
28. Mellanby RJ, Thomas D, Phillips JM, Cooke A (2007) Diabetes in non-obese diabetic mice is not associated with quantitative changes in CD4+ CD25+ Foxp3+ regulatory T cells. Immunology 12:115-128
29. Mahiou J, Walter U, Lepault F, Godeau F, Bach JF, Chatenoud L (2001) In vivo blockade of the Fas-Fas ligand pathway inhibits cyclophosphamide-induced diabetes in NOD mice. J Autoimmun 16:431-440
30. Kaminitz A, Mizrahi K, Yaniv I, Farkas DL, Stein J, Askenasy N (2009) Low levels of allogeneic but not syngeneic hematopoietic chimerism reverse autoimmune insulitis in prediabetic NOD mice. J Autoimmun 33:83-91
31. Pandiyan P, LenardoMJ (2008) The control of CD4+CD25+Foxp3+ regulatory T cell survival. Biol Direct 3:6
32. Yolcu ES, Kaminitz A, Ash S, Sagiv Y, Askenasy N, Yarkoni S (2008) Apoptosis as a mechanism of T regulatory cell homeostasis and suppression. Immunol Cell Biol 86:650-658
33. Gregori S, Giarratana N, Smiroldo S, Adorini L (2003) Dynamics of pathogenic and suppressor T cells in autoimmune diabetes development. J Immunol 171:4040-4047
34. Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY (2005) Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity 22:329-341
35. Fisson S, Darrasse-Jeze G, Litvinova E, Septier F, Klatzmann D, Liblau R, Salomon BL (2003) Continuous activation of autoreactive CD4+ CD25+ regulatory T cells in the steady state. J Exp Med 198:737-746
36. Knoechel B, Lohr J, Kahn E, Bluestone JA, Abbas AK (2005) Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen. J Exp Med 202:1375-1386
37. Kohm AP, McMahon JS, Podojil JR et al (2006) Cutting edge: Anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells. J Immunol 176:3301-3305
38. Stephens LA, Gray D, Anderton SM (2005) CD4+CD25+ regulatory T cells limit the risk of autoimmune disease arising from T cell receptor crossreactivity. Proc Natl Acad Sci USA 102:17418-17423
39. Askenasy N, Kaminitz A, Yarkoni S (2008) Mechanisms of T regulatory cell function. Autoimmun Rev 7:370-375
40. Rosignoli F, Torroba M, Juarranz Yet al (2006) VIP and tolerance induction in autoimmunity. Ann NY Acad Sci 1070:525-530
41. Battaglia M, Stabilini A, Draghici E et al (2006) Induction of tolerance in type 1 diabetes via both CD4+CD25+ T regulatory cells and T regulatory type 1 cells. Diabetes 55:1571-1580
42. Simon G, Parker M, Ramiya Vet al (2008) Murine antithymocyte globulin therapy alters disease progression in NOD mice by a time-dependent induction of immunoregulation. Diabetes 57: 405-414
43. Monti P, Scirpoli M, Maffi P et al (2008) Rapamycin monotherapy in patients with type 1 diabetes modifies CD4+CD25+ FOXP3+ regulatory T cells. Diabetes 57:2341-2347
44. Tian B, Hao J, Zhang Y et al (2009) Upregulating CD4+CD25+ FOXP3+ regulatory T cells in pancreatic lymph nodes in diabetic NOD mice by adjuvant immunotherapy. Transplantation 87:198-206
45. Tang Q, Henriksen KJ, Bi M et al (2004) In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med 199:1455-1465
46. Weber SE, Harbertson J, Godebu E et al (2006) Adaptive isletspecific regulatory CD4 T cells control autoimmune diabetes and mediate the disappearance of pathogenic Th1 cells in vivo. J Immunol 176:4730-4739
47. Willerford DM, Chen J, Ferry JA, Davidson L,Ma A, Alt FW(1995) Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment. Immunity 3:521-530
48. Alam A, Cohen LY, Aouad S, Sekaly RP (1999) Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells. J Exp Med 190:1879-1890
49. Yang W, Hussain S, Mi QS, Santamaria P, Delovitch TL (2004) Perturbed homeostasis of peripheral T cells elicits decreased susceptibility to anti-CD3-induced apoptosis in prediabetic nonobese diabetic mice. J Immunol 173:4407-4416
50. Decallonne B, van Etten E, Giulietti A, Casteels K, Overbergh L, Bouillon R, Mathieu C (2003) Defect in activation induced cell death in non-obese diabetic (NOD) T lymphocytes. J Autoimmun 20:219-226
51. You S, Belghith M, Cobbold S et al (2005) Autoimmune diabetes onset results from qualitative rather than quantitative agedependent changes in pathogenic T cells. Diabetes 54:1415-1422
52. D'Alise AM, Auyeung V, Feuerer M, Nishio J, Fontenot J, Benoist C, Mathis D (2008) The defect in T cell regulation in NOD mice is an effect on the T cell effectors. Proc Natl Acad Sci USA 105:19857-19862
53. Gregg RK, Jain R, Schoenleber SJ et al (2004) A sudden decline in active membrane bound TGF-beta impairs both T regulatory cell function and protection against autoimmune diabetes. J Immunol 173:7308-7316
54. Tritt M, Sgouroudis E, d'Hennezel E, Albanese A, Piccirillo CA (2008) Functional waning of naturally occurring CD4+ regulatory T cells contributes to the onset of autoimmune diabetes. Diabetes 57:113-123
55. Salomon B, Lenschow DJ, Rhee L, Ashourian N, Singh B, Sharpe A, Bluestone JA (2000) B7/CD28 costimulation is essential for the homeostasis of the CD4+ CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12:431-440
56. Wu AJ, Hua H, Munson SH, McDevitt HO (2002) Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice. Proc Natl Acad Sci USA 99:12287-12292