The impact of biological therapy on regulatory T cells in rheumatoid arthritis

Rheumatology (United Kingdom)

Volumn 54, Issue 5, 2014, Pages 768-775

  Byng Maddick, Rachel ^a   Ehrenstein, Michael R ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Anti TNF therapy; Biologic therapy; Regulatory T cells; Rheumatoid arthritis

Indexed keywords

ABATACEPT; ADALIMUMAB; B CELL ACTIVATING FACTOR; BIOLOGICAL MARKER; CD3 ANTIBODY; CD4 ANTIBODY; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; ETANERCEPT; FC RECEPTOR; GAMMA INTERFERON; GLUCOCORTICOID INDUCED TUMOR NECROSIS FACTOR RECEPTOR; GOLIMUMAB; INFLIXIMAB; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 17 ANTIBODY; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 6; INTERLEUKIN 6 ANTIBODY; RITUXIMAB; TOCILIZUMAB; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; TREGALIZUMAB; TUMOR NECROSIS FACTOR INHIBITOR;

ADOPTIVE TRANSFER; ANTIGEN PRESENTING CELL; AUTOIMMUNE DISEASE; B LYMPHOCYTE; BIOLOGICAL THERAPY; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; COMPLEMENT ACTIVATION; CYTOKINE PRODUCTION; DENDRITIC CELL; EFFECTOR CELL; ENZYME ACTIVATION; FRAMESHIFT MUTATION; HUMAN; HUMORAL IMMUNE DEFICIENCY; IPEX SYNDROME; MACROPHAGE; MONOCYTE; NATURAL KILLER CELL; NONHUMAN; PATHOGENESIS; PERSONALIZED MEDICINE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; RHEUMATOID ARTHRITIS; T LYMPHOCYTE ACTIVATION; TH17 CELL;

EID: 84929670608     PISSN: 14620324     EISSN: 14620332     Source Type: Journal    
DOI: 10.1093/rheumatology/keu487     Document Type: Review

References (90)

1. Prakken B, Ellen W, van Wijk F. Editorial: Quality or quantity? Unraveling the role of Treg cells in rheumatoid arthritis. Arthritis Rheum 2013;65:552-4.
2. Scheinecker C, Bonelli M, Smolen JS. Pathogenetic aspects of systemic lupus erythematosus with an emphasis on regulatory T cells. J Autoimmun 2010;35:269-75.
3. Free ME, Bunch DO, McGregor JA et al. Patients with antineutrophil cytoplasmic antibody-associated vasculitis have defective Treg cell function exacerbated by the presence of a suppression-resistant effector cell population. Arthritis Rheum 2013;65:1922-33.
4. Wing K, Sakaguchi S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 2010;11:7-13.
5. Jiang S. Regulatory T cells: from bench to bedside. Int Immunopharmacol 2009;9:515-7.
6. Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev Immunol 2003;3:253-7.
7. Sansom DM, Walker LS. The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology. Immunol Rev 2006;212:131-48.
8. Okamura T, Fujio K, Sumitomo S, Yamamoto K. Roles of LAG3 and EGR2 in regulatory T cells. Ann Rheum Dis 2012;71(Suppl 2):i96-100.
9. Rapetti L, Chavele KM, Evans CM, Ehrenstein MR. B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by regulatory T cells in rheumatoid arthritis. Ann Rheum Dis 2015;74:294-302.
10. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155:1151-64.
11. 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.
12. Gambineri E, Torgersen TR, Ochs HD. Immune dysregulation, polyendocrinopathy, enteropathy and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol 2003;15:430-5.
13. 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;27:20-1.
14. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365:2205-19.
15. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology 2012;51(Suppl 5):v3-11.
16. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005;5:953-64.
17. Torsteinsdottir I, Arvidson NG, Hallgren R, Hakansson L. Monocyte activation in rheumatoid arthritis (RA): increased integrin, Fc gamma and complement receptor expression and the effect of glucocorticoids. Clin Exp Immunol 1999; 115:554-60.
18. Liote F, Boval-Boizard B, Weill D, Kuntz D, Wautier JL. Blood monocyte activation in rheumatoid arthritis:increased monocyte adhesiveness, integrin expression, and cytokine release. Clin Exp Immunol 1996;106:13-9.
19. Kinne RW, Brauer R, Stuhlmuller B, Palombo-Kinne E, Burmester GR. Macrophages in rheumatoid arthritis. Arthritis Res 2000;2:189-202.
20. Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet 2007;370:1861-74.
21. Ehrenstein MR, Evans JG, Singh A et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFa therapy. J Exp Med 2004;200:277-85.
22. Flores-Borja F, Jury EC, Mauri C, Ehrenstein MR. Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritis. Proc Natl Acad Sci U S A 2008;105:19396-401.
23. Tivol EA, Borriello F, Schweitzer AN et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995;3:541-7.
24. Sarkar S, Fox DA. Regulatory T cell defects in rheumatoid arthritis. Arthritis Rheum 2007;56:710-3.
25. Miyara M, Ito Y, Sakaguchi S. TREG-cell therapies for autoimmune rheumatic diseases. Nat Rev Rheumatol 2014;10:543-51.
26. Ponchel F, Goeb V, Parmar R et al. An immunological biomarker to predict MTX response in early RA. Ann Rheum Dis 2014;73:2047-53.
27. Nadkarni S, Mauri C, Ehrenstein MR. Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta. J Exp Med 2007;204:33-9.
28. Moran EM, Mullan R, McCormick J et al. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies. Arthritis Res Ther 2009;11:R113.
29. Bettelli E, Carrier Y, Gao W et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006;441:235-8.
30. Koenen HJ, Smeets RL, Vink PM et al. Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 2008;112:2340-52.
31. McGovern JL, Nguyen DX, Notley CA et al. Th17 cells are restrained by Treg cells via the inhibition of interleukin-6 in patients with rheumatoid arthritis responding to anti-tumor necrosis factor antibody therapy. Arthritis Rheum 2012;64:3129-38.
32. Nie H, Zheng Y, Li R et al. Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNFalpha in rheumatoid arthritis. Nat Med 2013;19:322-8.
33. Chen X, Baumel M, Mannel DN, Howard OM, Oppenheim JJ. Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells. J Immunol 2007;179:154-61.
34. Grinberg-Bleyer Y, Saadoun D, Baeyens A et al. Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs. J Clin Invest 2010;120:4558-68.
35. Kleijwegt FS, Laban S, Duinkerken G et al. Critical role for TNF in the induction of human antigen-specific regulatory T cells by tolerogenic dendritic cells. J Immunol 2010;185:1412-8.
36. Chopra M, Riedel SS, Biehl M et al. Tumor necrosis factor receptor 2-dependent homeostasis of regulatory T cells as a player in TNF-induced experimental metastasis. Carcinogenesis 2013;34:1296-303.
37. Jamnitski A, Bartelds GM, Nurmohamed MT et al. The presence or absence of antibodies to infliximab or adalimumab determines the outcome of switching to etanercept. Ann Rheum Dis 2011;70:284-8.
38. Wehrens EJ, Mijnheer G, Duurland CL et al. Functional human regulatory T cells fail to control autoimmune inflammation due to PKB/c-akt hyperactivation in effector cells. Blood 2011;118:3538-48.
39. Cheng J, Phong B, Wilson DC, Hirsch R, Kane LP. Akt fine-tunes NF-kappaB-dependent gene expression during T cell activation. J Biol Chem 2011;286:36076-85.
40. Wehrens EJ, Vastert SJ, Mijnheer G et al. Anti-tumor necrosis factor alpha targets protein kinase B/c-Akt-induced resistance of effector cells to suppression in juvenile idiopathic arthritis. Arthritis Rheum 2013;65:3279-84.
41. Szalay B, Vasarhelyi B, Cseh A et al. The impact of conventional DMARD and biological therapies on CD4+ cell subsets in rheumatoid arthritis: a follow-up study. Clin Rheumatol 2014;33:175-85.
42. Tubach F, Salmon D, Ravaud P et al. Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: the three-year prospective French Research Axed on Tolerance of Biotherapies registry. Arthritis Rheum 2009;60:1884-94.
43. Ormerod LP, Milburn HJ, Gillespie S, Ledingham J, Rampton D. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-a treatment. Thorax 2005;60:800-5.
44. Edwards JC, Szczepanski L, Szechinski J et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;350:2572-81.
45. Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC. Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum 2006;54:613-20.
46. Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyand CM. T cell activation in rheumatoid synovium is B cell dependent. J Immunol 2001;167:4710-8.
47. Feuchtenberger M, Muller S, Roll P et al. Frequency of regulatory T cells is not affected by transient B cell depletion using anti-CD20 antibodies in rheumatoid arthritis. Open Rheumatol J 2008;2:81-8.
48. Hamel KM, Cao Y, Ashaye S et al. B cell depletion enhances T regulatory cell activity essential in the suppression of arthritis. J Immunol 2011;187:4900-6.
49. Sfikakis PP, Souliotis VL, Fragiadaki KG et al. Increased expression of the FoxP3 functional marker of regulatory T cells following B cell depletion with rituximab in patients with lupus nephritis. Clin Immunol 2007;123:66-73.
50. Stasi R, Cooper N, Del Poeta G et al. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood 2008;112:1147-50.
51. Zhao Y, Lutalo PM, Thomas JE et al. Circulating T follicular helper cell and regulatory T cell frequencies are influenced by B cell depletion in patients with granulomatosis with polyangiitis. Rheumatology 2014;53:621-30.
52. Ng LG, Sutherland AP, Newton R et al. B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells. J Immunol 2004;173:807-17.
53. Huard B, Arlettaz L, Ambrose C et al. BAFF production by antigen-presenting cells provides T cell co-stimulation. Int Immunol 2004;16:467-75.
54. Walters S, Webster KE, Sutherland A et al. Increased CD4+Foxp3+ T cells in BAFF-transgenic mice suppress T cell effector responses. J Immunol 2009;182:793-801.
55. Tanaka T, Kishimoto T. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci 2012;8:1227-36.
56. Madhok R, Crilly A, Watson J, Capell HA. Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann Rheum Dis 1993;52:232-4.
57. Nowell MA, Williams AS, Carty SA et al. Therapeutic targeting of IL-6 trans signaling counteracts STAT3 control of experimental inflammatory arthritis. J Immunol 2009;182:613-22.
58. Boe A, Baiocchi M, Carbonatto M, Papoian R, Serlupi-Crescenzi O. Interleukin 6 knock-out mice are resistant to antigen-induced experimental arthritis. Cytokine 1999;11:1057-64.
59. Takeuchi T, Tanaka Y, Amano K et al. Clinical, radiographic and functional effectiveness of tocilizumab for rheumatoid arthritis patients-REACTION 52-week study. Rheumatology 2011;50:1908-15.
60. Volpe E, Servant N, Zollinger R et al. A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol 2008;9:650-7.
61. Samson M, Audia S, Janikashvili N et al. Brief report: inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis. Arthritis Rheum 2012;64:2499-503.
62. Pesce B, Soto L, Sabugo F et al. Effect of interleukin-6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients. Clin Exp Immunol 2013;171:237-42.
63. Dooms H, Abbas AK. Revisiting the role of IL-2 in autoimmunity. Eur J Immunol 2010;40:1538-40.
64. Qureshi OS, Zheng Y, Nakamura K et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cellextrinsic function of CTLA-4. Science 2011;332:600-3.
65. Jain N, Nguyen H, Chambers C, Kang J. Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity. Proc Natl Acad Sci U S A 2010;107:1524-8.
66. Walker LS. Treg and CTLA-4: two intertwining pathways to immune tolerance. J Autoimmun 2013;45:49-57.
67. Wright GP, Notley CA, Xue SA et al. Adoptive therapy with redirected primary regulatory T cells results in antigenspecific suppression of arthritis. Proc Natl Acad Sci U S A 2009;106:19078-83.
68. Fallarino F, Grohmann U, Hwang KW et al. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 2003;4:1206-12.
69. Alvarez-Quiroga C, Abud-Mendoza C, Doniz-Padilla L et al. CTLA-4-Ig therapy diminishes the frequency but enhances the function of Treg cells in patients with rheumatoid arthritis. J Clin Immunol 2011;31:588-95.
70. Vogel I, Verbinnen B, Maes W et al. Foxp3+ regulatory T cells are activated in spite of B7-CD28 and CD40-CD40L blockade. Eur J Immunol 2013;43:1013-23.
71. Chatenoud L, Thervet E, Primo J, Bach JF. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci U S A 1994;91:123-7.
72. Notley CA, McCann FE, Inglis JJ, Williams RO. ANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces sustained amelioration of collageninduced arthritis. Arthritis Rheum 2010;62:171-8.
73. Chatenoud L, Baudrihaye MF, Kreis H et al. Human in vivo antigenic modulation induced by the anti-T cell OKT3 monoclonal antibody. Eur J Immunol 1982;12:979-82.
74. Ablamunits V, Bisikirska B, Herold KC. Acquisition of regulatory function by human CD8(+) T cells treated with anti-CD3 antibody requires TNF. Eur J Immunol 2010;40:2891-901.
75. Deal watch: boosting TRegs to target autoimmune disease. Nat Rev Drug Discov 2011;10:566.
76. Duarte J, Agua-Doce A, Oliveira VG, Fonseca JE, Graca L. Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice. PLOS ONE 2010;5:e10558.
77. Czeloth N, Dälken B, Engling A et al. Selective activation of naturally occurring regulatory T cells (TREGs) by the monoclonal antibody BT-061 as a novel therapeutic opportunity:pre-clinical and early clinical results [abstract OP0138]. Ann Rheum Dis 2010;69 Suppl. 3):99.
78. Abufarag A, Aigner S, Czeloth N et al. Selective activation of naturally occurring regulatory T cells (Tregs) by monoclonal antibody (mAb) BT-061. Markers of clinical activity and early Phase II results in patients with rheumatoid arthritis (RA). Program Book of the ACR/ARHP Scientific Meeting, Atlanta, GA, 2010. Abstract 1125. ACR/ Association of Rheumatology Health Professionals.
79. Uherek C, Engling A, Daelken B et al. The novel regulatory T cell (Treg) agonistic monoclonal antibody (mAb) tregalizumab (BT-061): further characterization of mechanism of action, epitope binding, and clinical effects in patients with rheumatoid arthritis. http://www.biotest.de [in German] 2011 (19 January 2015, date last accessed).
80. Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum 2009; 60:1647-56.
81. Lubberts E, Joosten LA, Oppers B et al. IL-1-independent role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis. J Immunol 2001;167:1004-13.
82. van den Berg WB, Miossec P. IL-17 as a future therapeutic target for rheumatoid arthritis. Nat Rev Rheumatol 2009;5:549-53.
83. Papp KA, Langley RG, Sigurgeirsson B et al. Efficacy and safety of secukinumab in the treatment of moderateto- severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study. Brit J Dermatol 2013;168:412-21.
84. Papp KA, Leonardi C, Menter A et al. Brodalumab, an antiinterleukin-17-receptor antibody for psoriasis. N Engl J Med 2012;366:1181-9.
85. Genovese MC, Durez P, Richards HB et al. Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann Rheum Dis 2013;72:863-9.
86. Martin DA, Churchill M, Flores-Suarez L et al. A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early clinical response of brodalumab, a human anti-IL-17R antibody, in methotrexate-resistant rheumatoid arthritis. Arthritis Res Ther 2013;15:R164.
87. Takahashi T, Kuniyasu Y, Toda M et al. Immunologic selftolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 1998;10:1969-80.
88. Koreth J, Matsuoka K, Kim HT et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med 2011;365:2055-66.
89. Saadoun D, Rosenzwajg M, Joly F et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med 2011;365:2067-77.
90. Long SA, Rieck M, Sanda S et al. Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs beta-cell function. Diabetes 2012;61:2340-8.