Regulatory T cells in the control of inflammatory demyelinating diseases of the central nervous system

Current Opinion in Neurology

Volumn 21, Issue 3, 2008, Pages 248-254

  Anderton, Stephen M ^a   Liblau, Roland S ^b  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b TOULOUSE UNIVERSITY HOSPITAL   (France)

Author keywords

Autoimmune encephalomyelitis; Autoimmunity; Foxp3; Multiple sclerosis; Regulatory T cells

Indexed keywords

TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA;

ALLERGIC ENCEPHALOMYELITIS; BIOLOGICAL ACTIVITY; CD4+ CD25+ T LYMPHOCYTE; DEMYELINATING DISEASE; ENCEPHALITIS; HUMAN; IMMUNE RESPONSE; IMMUNOTHERAPY; MULTIPLE SCLEROSIS; NONHUMAN; REGULATORY T LYMPHOCYTE; REVIEW; TARGET CELL; THYMUS;

ANIMALS; CENTRAL NERVOUS SYSTEM DISEASES; DEMYELINATING DISEASES; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; HUMANS; IMMUNOTHERAPY; MULTIPLE SCLEROSIS; T-LYMPHOCYTES, REGULATORY;

EID: 43249128068     PISSN: 13507540     EISSN: None     Source Type: Journal    
DOI: 10.1097/WCO.0b013e3282febf58     Document Type: Review

References (75)

1. Cassan C, Liblau RS. Immune tolerance and control of CNS autoimmunity: from animal models to MS patients. J Neurochem 2007; 100:883-892.
2. + natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 2006; 212:8-27.
3. Gavin MA, Rasmussen JP, Fontenot JD, et al. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 2007; 445:771-775.
4. Williams LM, Rudensky AY. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat Immunol 2007; 8:277-284.
5. Fontenot JD, Rasmussen JP, Williams LM, et al. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005; 22:329-341.
6. Kim JM, Rasmussen JP, Rudensky AY. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol 2007; 8:191-197.
7. + regulatory T cells induces a scurfy-like disease. J Exp Med 2007; 204:57-63.
8. + peptide-MHC multimers to track the development of a Treg response during active EAE. MOG-reactive Tregs were present in the 'naïve' repertoire, were expanded in the lymph node after immunization and migrated to the CNS during EAE. The Treg/Teffector ratio increased in the CNS during recovery. The authors suggest that Treg-mediated suppression is inhibited in the CNS due to high levels of proinflammatory cytokines (TNF-α and IL-6) at peak of disease.
9. Gavin MA, Torgerson TR, Houston E, et al. Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc Natl Acad Sci U S A 2006; 103:6659-6664.
10. 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; 27:20-21.
11. Wildin RS, Ramsdell F, Peake J, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 2001; 27:18-20.
12. Jordan MS, Boesteanu A, Reed AJ, et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol 2001; 2:301-306.
13. Romagnoli P, Hudrisier D, van Meerwijk JP, et al. Preferential recognition of self antigens despite normal thymic deletion of CD4(+)CD25(+) regulatory T cells. J Immunol 2002; 168:1644-1648.
14. + regulatory T cells specific for a neo-self-antigen develop at the double-positive thymic stage. Proc Natl Acad Sci U S A 2006; 103:8453-8458.
15. + regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 2007; 204:1757-1764.
16. Benson MJ, Pino-Lagos K, Rosemblatt M, Noelle RJ. All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J Exp Med 2007; 204:1765-1774.
17. Sun CM, Hall JA, Blank RB, et al. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 2007; 204:1775-1785.
18. von Boehmer H. Oral tolerance: is it all retinoic acid? J Exp Med 2007; 204:1737-1739.
19. Pandiyan P, Zheng L, Ishihara S, et al. CD4(+)CD25(+)Foxp3(+) regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4(+) T cells. Nat Immunol 2007; 8:1353-1362.
20. Cao X, Cai SF, Fehniger TA, et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 2007; 27:635-646.
21. + Tregs in the blood.
22. Deaglio S, Dwyer KM, Gao W, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 2007; 204:1257-1265.
23. - precursor cells in the absence of interleukin 10. Nat Immunol 2007; 8:931-941.
24. + T cells that will suppress CNS inflammation.
25. + Treg can interact with dendritic cells endowing them with the capacity to drive the generation of IL-10 producing foxp3-negative cells through dendritic cells production of IL-27.
26. O'Connor RA, Anderton SM. Foxp3(+) regulatory T cells in the control of experimental CNS autoimmune disease. J Neuroimmunol 2008; 193:1-11.
27. + T regulatory cells. J Immunol 2006; 176:3301-3305.
28. + regulatory T cells limit the risk of autoimmune disease arising from T cell receptor crossreactivity. Proc Natl Acad Sci U S A 2005; 102:17418-17423.
29. Anderton SM. Avoiding autoimmune disease: T cells know their limits. Trends Immunol 2006; 27:208-214.
30. + regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 2004; 101:15434-15439.
31. + regulatory T cells contribute to gender differences in susceptibility to experimental autoimmune encephalomyelitis. J Immunol 2005; 175:5591-5595.
32. + regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J Immunol 2002; 169:4712-4716.
33. + regulatory T cells. Int Immunol 2004; 16:249-256.
34. + T cells and dendritic cells in vivo. J Exp Med 2006; 203:505-511.
35. + regulatory cells within the central nervous system. J Immunol 2005; 175:3025-3032.
36. + infiltrate), indicating that Tregs are naturally attracted to sites of inflammation. These Tregs were rapidly proliferating specifically in the CNS, but appeared not to recognize MOG(35-55). CNS Tregs could suppress MOG-induced IFN-γ production by the CNS effector cells, but did not block IL-17 production.
37. Bettelli E, Das MP, Howard ED, et al. IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice. J Immunol 1998; 161:3299-3306.
38. + T cells. Int Immunol 2006; 18:495-503.
39. Matsumoto Y, Sakuma H, Kohyama K, Park IK. Paralysis of CD4(+)CD25(+) regulatory T cell response in chronic autoimmune encephalomyelitis. J Neuroimmunol 2007; 187:44-54.
40. Gartner D, Hoff H, Gimsa U, et al. CD25 regulatory T cells determine secondary but not primary remission in EAE: impact on long-term disease progression. J Neuroimmunol 2006; 172:73-84.
41. + regulatory T cells. J Immunol 2006; 177:1552-1560.
42. + T regulatory cells. Eur J Immunol 2006; 36:671-680.
43. + Tregs. J Clin Invest 2006; 116:2434-2441.
44. McMahon EJ, Bailey SL, Castenada CV, et al. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat Med 2005; 11:335-339.
45. + T(H)-17 cells in relapsing EAE. Nat Immunol 2007; 8:172-180.
46. + dendritic cells isolated from the CNS at different stages of EAE. Dendritic cells isolated early in EAE were effective at driving the in-vivo differentiation of naïve MOG-reactive TCR transgenic T cells into Th1 and Th17 cells. Nevertheless, dendritic cells isolated immediately prior to EAE remission were less effective at this and could be used as antigen presenting cells for in-vitro Treg suppression assays. These results suggest that the function of CNS dendritic cells may alter, impacting on the disease course of EAE.
47. Liu L, Huang D, Matsui M, et al. Severe disease, unaltered leukocyte migration, and reduced IFN-gamma production in CXCR3-/- mice with experimental autoimmune encephalomyelitis. J Immunol 2006; 176:4399-4409.
48. + cells, with a more diffuse appearance throughout the CNS white matter. Thus CXCR3 ligands (CXCL9, CXCL10 or CXCL11) may serve important roles in Treg attraction to the CNS and their appropriate distribution close to CNS effector cells.
49. + regulatory T cells in patients with multiple sclerosis. J Exp Med 2004; 199:971-979.
50. +CD25 high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur J Immunol 2005; 35:3343-3352.
51. high cells from MS patients. They suggest that these Treg defects are partially corrected upon IFN-β treatment.
52. + regulatory T cells in the cerebrospinal fluid but not in the blood of multiple sclerosis patients. Clin Exp Immunol 2007; 147:412-418.
53. + T cells are not detected in brain lesions whereas they are clearly present in secondary lymphoid organs. If the latter result is confirmed in postmortem and also biopsy material, this would highlight a clear difference between the human disease and the EAE model.
54. Chen X, Oppenheim JJ, Winkler-Pickett RT, et al. Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+)CD4(+)CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur J Immunol 2006; 36:2139-2149.
55. + cell numbers through their increased proliferation.
56. Jee Y, Piao WH, Liu R, et al. CD4(+)CD25(+) regulatory T cells contribute to the therapeutic effects of glatiramer acetate in experimental autoimmune encephalomyelitis. Clin Immunol 2007; 125:34-42.
57. + regulatory T-cell function: an ex vivo and in vitro longitudinal study in relapsing-remitting multiple sclerosis. J Neuroimmuol 2007; 182:204-211.
58. hight T regulatory cells and their IL-10 production in multiple sclerosis. J Neuroimmunol 2003; 144:125-131.
59. + T cells in multiple sclerosis. J Immunol 2006; 176:7119-7129.
60. + regulatory T cells by copolymer-I through activation of transcription factor Foxp3. Proc Natl Acad Sci U S A 2005; 102:6449-6454.
61. Cox AL, Thompson SAJ, Jones JL, et al. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol 2005; 35:3332-3342.
62. + T helper cells. Eur J Immunol 2004; 34:1303-1311.
63. bright natural killer cells mediate immunomodulatory effects of IL-2Rα-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A 2006; 103:5941-5946.
64. + regulatory T-cell pool is present in renal transplant recipients. Am J Transplant 2007; 7:249-255.
65. + T reg cells. J Exp Med 2006; 203:1701-1711.
66. + regulatory T cells selected in vitro from a polyclonal repertoire. Eur J Immunol 2006; 36:817-827.
67. + regulatory T cells from nonobese diabetic mice. J Immunol 2005; 175:3053-3059.
68. Kretschmer K, Apostolou I, Hawiger D, et al. Inducing and expanding regulatory T cell populations by foreign antigen. Nat Immunol 2005; 6:1219-1227.
69. Liu Y, Teige I, Birnir B, Issazadeh-Navikas S. Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE. Nat Med 2006; 12:518-525.
70. Roncarolo MG, Battaglia M. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Nat Rev Immunol 2007; 7:585-598. This is a comprehensive and thoughtful review on the current status of adoptive cell therapy using regulatory T-cell populations in humans. The limits and difficulties of such an approach are clearly underlined.
71. + regulatory T cells occur in the absence of inflammatory signals. J Immunol 2008; 180:327-334.
72. + T cells. Blood 2008; 111:453-462. This study reports that murine Tregs have a preferential capacity for clonal expansion in response to antigen in the presence of rapamycin. This correlated with the activation of signaling pathways that are not blocked by rapamycin (unlike conventional T cells). These data may have implications for the rational use of rapamycin in combination therapies to specifically select for disease-relevant Treg expansion.
73. Duplan V, Beriou G, Heslan JM, et al. LF 15-0195 treatment protects against central nervous system autoimmunity by favoring the development of Foxp3-expressing regulatory CD4 T cells. J Immunol 2006; 176:839-847.
74. Ochi H, Abraham M, Ishikawa H, et al. Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4(+)CD25(-)LAP(+) T cells. Nat Med 2006; 12:627-635.
75. Piaggio E, Mars L, Cassan C, et al. Multimerized T cell epitopes protect from experimental autoimmune diabetes by inducing dominant tolerance. Proc Natl Acad Sci U S A 2007; 104:9393-9398.