Regulatory T cells as therapeutic targets in rheumatoid arthritis

Nature Reviews Rheumatology

Volumn 5, Issue 10, 2009, Pages 560-565

  Esensten, Jonathan H ^a   Wofsy, David ^a   Bluestone, Jeffrey A ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABATACEPT; ANTIRHEUMATIC AGENT; ATLIZUMAB; BELATACEPT; EVEROLIMUS; HYDROXYCHLOROQUINE; INFLIXIMAB; INTERLEUKIN 2; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR BLOCKER; IRS 954; MAMMALIAN TARGET OF RAPAMYCIN; METHOTREXATE; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; RAPAMYCIN; RECEPTOR BLOCKING AGENT; RECOMBINANT INTERLEUKIN 2; TOLL LIKE RECEPTOR; TRICHOSTATIN A; TUMOR NECROSIS FACTOR ANTIBODY; UNCLASSIFIED DRUG; VORINOSTAT;

AUTOIMMUNE DISEASE; CD4+ CD25+ T LYMPHOCYTE; CUTANEOUS T CELL LYMPHOMA; DRUG APPROVAL; DRUG MECHANISM; DRUG RECEPTOR BINDING; GLOMERULONEPHRITIS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IMMUNOPATHOGENESIS; JUVENILE RHEUMATOID ARTHRITIS; LYMPHOCYTE COUNT; LYMPHOCYTE FUNCTION; LYMPHOCYTE PROLIFERATION; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REMISSION; REVIEW; RHEUMATOID ARTHRITIS; TARGET CELL; TH17 CELL;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; BLOOD COMPONENT TRANSFUSION; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; DRUG DELIVERY SYSTEMS; HUMANS; T-LYMPHOCYTES, REGULATORY;

EID: 70349969840     PISSN: 17594790     EISSN: 17594804     Source Type: Journal    
DOI: 10.1038/nrrheum.2009.183     Document Type: Review

References (89)

1. Tang, Q. & Bluestone, J. A. Regulatory T-cell physiology and application to treat autoimmunity. Immunol. Rev. 212, 217-237 (2006).
2. Liu, W. et al. CD127 expression inversely correlates with FOXP3 and suppressive function of human CD4+ TREG cells. J. Exp. Med. 203, 1701-1711 (2006).
3. Putnam, A. L. et al. Expansion of human regulatory T-cells from patients with type 1 diabetes. Diabetes 58, 652-662 (2009).
4. + T regulatory cell-mediated suppression. Immunity 30, 636-645 (2009).
5. + regulatory T cells in autoimmunity: immunopathogenesis and therapeutic implications. Am. J. Pathol. 174, 1575-1587 (2009).
6. + T cell receptors. Immunity 21, 267-277 (2004).
7. + regulatory T cells. Nat. Immunol. 4, 330-336 (2003).
8. Bacchetta, R. et al. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J. Clin. Invest. 116, 1713-1722 (2006).
9. Wildin, R. S. et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 27, 18-20 (2001).
10. Mazzolari, E. et al. A new case of IPEX receiving bone marrow transplantation. Bone Marrow Transplant. 35, 1033-1034 (2005).
11. Dorsey, M. J., Petrovic, A., Morrow, M. R., Dishaw, L. J. & Sleasman, J. W. FOXP3 expression following bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. Immunol. Res. 44, 179-184 (2009).
12. Baud, O. et al. Treatment of the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) by allogeneic bone marrow transplantation. N. Engl. J. Med. 344, 1758-1762 (2001).
13. Rao, A. et al. Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. Blood 109, 383-385 (2007).
14. high FOXP3-positive T cells in IPEX syndrome after nonmyeloablative hematopoietic stem cell transplantation. Blood 113, 5689-5691 (2009).
15. Wang, J., Wicker, L. S. & Santamaria, P. IL-2 and its high-affinity receptor: genetic control of immunoregulation and autoimmunity. Semin. Immunol. doi:10.1016/j.smim.2009.04.004.
16. +FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-β dependent but does not confer a regulatory phenotype. Blood 110, 2983-2990 (2007).
17. + T cells expressing the FOXP3 transcription factor. Immunity 30, 899-911 (2009).
18. Floess, S. et al. Epigenetic control of the FOXP3 locus in regulatory T cells. PLoS Biol. 5, e38 (2007).
19. + T cell lineage differentiation. Immunity 30, 646-655 (2009).
20. Wieczorek, G. et al. 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 (2009).
21. Brusko, T. M., Putnam, A. L. & Bluestone, J. A. Human regulatory T cells: role in autoimmune disease and therapeutic opportunities. Immunol. Rev. 223, 371-390 (2008).
22. high regulatory cells in human peripheral blood. J. Immunol. 167, 1245-1253 (2001).
23. REG function when cells expressing IL-7 receptor α-chain are excluded from the analysis. J. Clin. Invest. 118, 3411-3419 (2008).
24. + regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum. 50, 2775-2785 (2004).
25. Ehrenstein, M. R. et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNF-α therapy. J. Exp. Med. 200, 277-285 (2004).
26. + T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis. Clin. Exp. Immunol. 140, 360-367 (2005).
27. Flores-Borja, F., Jury, E. C., Mauri, C. & Ehrenstein, M. R. Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritis. Proc. Natl Acad. Sci. USA 105, 19396-19401 (2008).
28. + T cells from the target organ of patients with rheumatoid arthritis. Eur. J. Immunol. 33, 215-223 (2003).
29. high regulatory T cell population in peripheral blood. Rheumatology (Oxford) 45, 1210-1217 (2006).
30. REG cells at sites of inflammation. Immunity 29, 511-512 (2008).
31. Tang, Q. et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity 28, 687-697 (2008).
32. hi T-regulatory cells. Blood 108, 253-261 (2006).
33. + regulatory T cells. J. Immunol. 181, 7350-7355 (2008).
34. Nadkarni, S., Mauri, C. & Ehrenstein, M. R. Anti-TNF-α therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-β. J. Exp. Med. 204, 33-39 (2007).
35. Emery, P. et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann. Rheum. Dis. 67, 1516-1523 (2008).
36. Maini, R. N. et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 54, 2817-2829 (2006).
37. Jones, G. et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann. Rheum. Dis. doi:ard.2008.105197v1.
38. Genovese, M. C. et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 58, 2968-2980 (2008).
39. + T cell-mediated suppression by dendritic cells. Science 299, 1033-1036 (2003).
40. Chen, X. et al. Blockade of interleukin-6 signaling augments regulatory T cell reconstitution and attenuates the severity of graft versus host disease. Blood 114, 891-900 (2009).
41. H17 cells. Nature 454, 350-352 (2008).
42. +CD25 T cells. J. Immunol. 179, 2041-2045 (2007).
43. Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A. & Sallusto, F. Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nat. Immunol. 8, 942-949 (2007).
44. + regulatory T cell-mediated suppression in rheumatoid arthritis. Arthritis Rheum. 56, 732-742 (2007).
45. Linsley, P. S. & Nadler, S. G. The clinical utility of inhibiting CD28-mediated costimulation. Immunol. Rev. 229, 307-321 (2009).
46. Bluestone, J. A. et al. The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation. Am. J. Transplant. 8, 2086-2096 (2008).
47. + regulatory T cells. J. Immunol. 171, 3348-3352 (2003).
48. Genovese, M. C. et al. Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy. Ann. Rheum. Dis. 67, 547-554 (2008).
49. Genovese, M. C. et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor α inhibition. N. Engl. J. Med. 353, 1114-1123 (2005).
50. Thomson, A. W., Turnquist, H. R. & Raimondi, G. Immunoregulatory functions of mTOR inhibition. Nat. Rev. Immunol. 9, 324-337 (2009).
51. + regulatory T cells of both healthy subjects and type 1 diabetic patients. J. Immunol. 177, 8338-8347 (2006).
52. REG) and effector T cells to rapamycin. PLoS One 4, e5994 (2009).
53. Iwasaki, A. & Medzhitov, R. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5, 987-995 (2004).
54. REG cells? A double-edged sword in immunity to tumours. Oncogene 27, 168-180 (2008).
55. REGs: to suppress or not to suppress? Immunology 124, 445-452 (2008).
56. Hall, J. A. et al. Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity 29, 637-649 (2008).
57. Brentano, F., Schorr, O., Gay, R. E., Gay, S. & Kyburz, D. RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3. Arthritis Rheum. 52, 2656-2665 (2005).
58. Kyburz, D., Brentano, F. & Gay, S. Mode of action of hydroxychloroquine in RA - evidence of an inhibitory effect on Toll-like receptor signaling. Nat. Clin. Pract. Rheumatol. 2, 458-459 (2006).
59. Barrat, F. J., Meeker, T., Chan, J. H., Guiducci, C. & Coffman, R. L. Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms. Eur. J. Immunol. 37, 3582-3586 (2007).
60. Tao, R. et al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat. Med. 13, 1299-1307 (2007).
61. + regulatory T cells with histone deacetylase inhibitors. Cell. Immunol. 257, 97-104 (2009).
62. + regulatory T cells differentiate into IL-17-producing cells. Blood 112, 2340-2352 (2008).
63. Mann, B. S., Johnson, J. R., Cohen, M. H., Justice, R. & Pazdur, R. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 12, 1247-1252 (2007).
64. + regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J. Exp. Med. 201, 723-735 (2005).
65. REG cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. J. Exp. Med. 206, 751-760 (2009).
66. + T-cell pool and tumor trafficking in patients with ovarian carcinoma. Cancer Res. 67, 7487-7494 (2007).
67. Verburg, R. J. et al. High-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with rheumatoid arthritis: results of an open study to assess feasibility, safety, and efficacy. Arthritis Rheum. 44, 754-760 (2001).
68. Teng, Y. K. et al. Long-term followup of health status in patients with severe rheumatoid arthritis after high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation. Arthritis Rheum. 52, 2272-2276 (2005).
69. Snowden, J. A. et al. Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR. J. Rheumatol. 31, 482-488 (2004).
70. De Kleer, I. M. et al. Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: analysis of clinical effects, mortality, and transplant related morbidity. Ann. Rheum. Dis. 63, 1318-1326 (2004).
71. Brinkman, D. M. et al. Autologous stem cell transplantation in children with severe progressive systemic or polyarticular juvenile idiopathic arthritis: long-term follow-up of a prospective clinical trial. Arthritis Rheum. 56, 2410-2421 (2007).
72. Snowden, J. A., Kapoor, S. & Wilson, A. G. Stem cell transplantation in rheumatoid arthritis. Autoimmunity 1, doi:10.1080/ 08916930802198550.
73. + regulatory T cell pool by radioresistant host cells in scurfy bone marrow chimeras. Proc. Natl Acad. Sci. USA 104, 8959-8964 (2007).
74. Brusko, T. & Bluestone, J. Clinical application of regulatory T cells for treatment of type 1 diabetes and transplantation. Eur. J. Immunol. 38, 931-934 (2008).
75. REG cryopreservation. PLoS ONE 3, e3161 (2008).
76. + regulatory T cells from nonobese diabetic mice. J. Immunol. 175, 3053-3059 (2005).
77. Tang, Q. et al. In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J. Exp. Med. 199, 1455-1465 (2004).
78. Scalapino, K. J., Tang, Q., Bluestone, J. A., Bonyhadi, M. L. & Daikh, D. I. Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells. J. Immunol. 177, 1451-1459 (2006).
79. + regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol. 169, 4712-4716 (2002).
80. + regulatory T cells. J. Immunol. 170, 3939-3943 (2003).
81. Morgan, R. A. et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314, 126-129 (2006).
82. Arbour, N. et al. A new clinically relevant approach to expand myelin specific T cells. J. Immunol. Meth. 310, 53-61 (2006).
83. Beriou, G. et al. IL-17-producing human peripheral regulatory T cells retain suppressive function. Blood 113, 4240-4249 (2009).
84. + regulatory T cells in humans. Proc. Natl Acad. Sci. USA 106, 4793-4798 (2009).
85. Zhou, X. et al. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. doi:10.1038/ni.1774.
86. H17 cells. J. Exp. Med. 204, 1849-1861 (2007).
87. Evans, H. G., Suddason, T., Jackson, I., Taams, L. S. & Lord, G. M. Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes. Proc. Natl Acad. Sci. USA 104, 17034-17039 (2007).
88. Riley, J. L., June, C. H. & Blazar, B. R. Human T regulatory cell therapy: take a billion or so and call me in the morning. Immunity 30, 656-665 (2009).
89. Umbilical cord blood T-regulatory cell infusion followed by donor umbilical cord blood transplant in treating patients with high-risk leukemia or other hematologic diseases. Clinical Trials.gov [online] http://clinicaltrials.gov/ct2/show/NCT00376519 (2009).