Disturbed regulatory T cell homeostasis in multiple sclerosis

Trends in Molecular Medicine

Volumn 16, Issue 2, 2010, Pages 58-68

  Venken, Koen ^a,b   Hellings, Niels ^a   Liblau, Roland ^c   Stinissen, Piet ^a  

^a HASSELT UNIVERSITY   (Belgium)

^b GHENT UNIVERSITY HOSPITAL   (Belgium)

^c TOULOUSE UNIVERSITY HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ALEMTUZUMAB; BETA INTERFERON; CD1D ANTIGEN; CD28 ANTIGEN; CD31 ANTIGEN; CD4 ANTIGEN; CD45 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DACLIZUMAB; GAMMA INTERFERON; GLATIRAMER; GLUCOCORTICOID; GRANZYME; HLA E ANTIGEN; HLA G ANTIGEN; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 2 RECEPTOR BETA; INTERLEUKIN 4; INTERLEUKIN 7 RECEPTOR; L SELECTIN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; NATALIZUMAB; NEUROVAX; PEPTIDE VACCINE; PERFORIN; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AUTOIMMUNITY; CD4+ CD25+ T LYMPHOCYTE; CHRONIC DISEASE; HOMEOSTASIS; HUMAN; IMMUNOREGULATION; MEMORY CELL; MULTIPLE SCLEROSIS; NATURAL KILLER T CELL; NONHUMAN; REGULATORY T LYMPHOCYTE; RELAPSE; REMISSION; REVIEW;

EID: 76249094369     PISSN: 14714914     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.molmed.2009.12.003     Document Type: Review

References (102)

1. Compston A., and Coles A. Multiple sclerosis. Lancet 372 (2008) 1502-1517
2. Jiang H., and Chess L. Regulation of immune responses by T cells. N. Engl. J. Med. 354 (2006) 1166-1176
3. Sakaguchi S., et al. 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. 155 (1995) 1151-1164
4. Kim J.M., et al. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8 (2007) 191-197
5. Viglietta V., et al. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med. 199 (2004) 971-979
6. Haas J., et al. Reduced suppressive effect of CD4(+)CD25(high) regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur. J. Immunol. 35 (2005) 3343-3352
7. Venken K., et al. Secondary progressive in contrast to relapsing-remitting multiple sclerosis patients show a normal CD4+CD25+ regulatory T-cell function and FOXP3 expression. J. Neurosci. Res. 83 (2006) 1432-1446
8. Venken K., et al. Natural naive CD4+CD25+CD127low regulatory T cell (Treg) development and function is disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. J. Immunol. 180 (2008) 6411-6420
9. Haas J., et al. Prevalence of newly generated naive regulatory T cells (Treg) is critical for Treg suppressive function and determines Treg dysfunction in multiple sclerosis. J. Immunol. 179 (2007) 1322-1330
10. Sospedra M., and Martin R. Immunology of multiple sclerosis. Annu. Rev. Immunol. 23 (2005) 683-747
11. Hafler D.A., et al. Multiple sclerosis. Immunol. Rev. 204 (2005) 208-231
12. Rovaris M., et al. Secondary progressive multiple sclerosis: current knowledge and future challenges. Lancet Neurol. 5 (2006) 343-354
13. Lassmann H., et al. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 17 (2007) 210-218
14. Lucchinetti C., et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47 (2000) 707-717
15. Breij E.C., et al. Homogeneity of active demyelinating lesions in established multiple sclerosis. Ann. Neurol. 63 (2008) 16-25
16. 't Hart B.A., et al. Multiple sclerosis - a response-to-damage model. Trends Mol. Med. 15 (2009) 235-244
17. Ramagopalan S.V., et al. Multiple sclerosis and the major histocompatibility complex. Curr. Opin. Neurol. 22 (2009) 219-225
18. Hafler D.A., et al. Risk alleles for multiple sclerosis identified by a genome-wide study. N. Engl. J. Med. 357 (2007) 851-862
19. Junker A., et al. Multiple sclerosis: T-cell receptor expression in distinct brain regions. Brain 130 (2007) 2789-2799
20. Marik C., et al. Lesion genesis in a subset of patients with multiple sclerosis: a role for innate immunity?. Brain 130 (2007) 2800-2815
21. Hendriks J.J., et al. Macrophages and neurodegeneration. Brain Res. Brain Res. Rev. 48 (2005) 185-195
22. Zappulla J.P., et al. Mast cells: new targets for multiple sclerosis therapy?. J. Neuroimmunol. 131 (2002) 5-20
23. Martin R., et al. Immunological aspects of demyelinating diseases. Annu. Rev. Immunol. 10 (1992) 153-187
24. Hellings N., et al. Insights into the immunopathogenesis of multiple sclerosis. Immunol. Res. 25 (2002) 27-51
25. O'Garra A. Interleukin-12 and up: functions of T helper subsets resulting from differential cytokine production. Res. Immunol. 148 (1997) 413-416
26. Cua D.J., et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421 (2003) 744-748
27. Korn T., et al. IL-17 and Th17 Cells. Annu. Rev. Immunol. 27 (2009) 485-517
28. Zhou L., and Littman D.R. Transcriptional regulatory networks in Th17 cell differentiation. Curr. Opin. Immunol. 21 (2009) 146-152
29. Haak S., et al. IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. J. Clin. Invest 119 (2009) 61-69
30. Matusevicius D., et al. Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult. Scler. 5 (1999) 101-104
31. Tzartos J.S., et al. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am. J. Pathol. 172 (2007) 146-155
32. Kebir H., et al. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat. Med. 13 (2007) 1173-1175
33. Kroenke M.A., et al. IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J. Exp. Med. 205 (2008) 1535-1541
34. Yang X.O., et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29 (2008) 44-56
35. Sorensen T.L., and Sellebjerg F. Distinct chemokine receptor and cytokine expression profile in secondary progressive MS. Neurology 57 (2001) 1371-1376
36. Balashov K.E., et al. Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand. Proc. Natl. Acad. Sci. U. S. A. 94 (1997) 599-603
37. Boxel-Dezaire A.H., et al. Decreased interleukin-10 and increased interleukin-12p40 mRNA are associated with disease activity and characterize different disease stages in multiple sclerosis. Ann. Neurol. 45 (1999) 695-703
38. Anderton S.M., and Liblau R.S. Regulatory T cells in the control of inflammatory demyelinating diseases of the central nervous system. Curr. Opin. Neurol. 21 (2008) 248-254
39. Zhang X., et al. IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells. Int. Immunol. 16 (2004) 249-256
40. Kohm A.P., et al. Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol. 169 (2002) 4712-4716
41. Kumar M., et al. CD4+CD25+FoxP3+ T lymphocytes fail to suppress myelin basic protein-induced proliferation in patients with multiple sclerosis. J. Neuroimmunol. 180 (2006) 178-184
42. Huan J., et al. Decreased FOXP3 levels in multiple sclerosis patients. J. Neurosci. Res. 81 (2005) 45-52
43. Venken K., et al. Compromised CD4+ CD25(high) regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. Immunology 123 (2008) 79-89
44. Thewissen M., and Stinissen P. New concepts on the pathogenesis of autoimmune diseases: a role for immune homeostasis, immunoregulation, and immunosenescence. Crit. Rev. Immunol. 28 (2008) 363-376
45. Hug A., et al. Thymic export function and T cell homeostasis in patients with relapsing remitting multiple sclerosis. J. Immunol. 171 (2003) 432-437
46. Thewissen M., et al. Analyses of immunosenescent markers in patients with autoimmune disease. Clin. Immunol. 123 (2007) 209-218
47. Michel L., et al. Patients with relapsing-remitting multiple sclerosis have normal Treg function when cells expressing IL-7 receptor alpha-chain are excluded from the analysis. J. Clin. Invest. 118 (2008) 3411-3419
48. Oh U., et al. Reduced Foxp3 protein expression is associated with inflammatory disease during human t lymphotropic virus type 1 Infection. J. Infect. Dis. 193 (2006) 1557-1566
49. Bacchetta R., et al. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J. Clin. Invest. 116 (2006) 1713-1722
50. De Jager P.L., et al. The role of the CD58 locus in multiple sclerosis. Proc. Natl. Acad. Sci. U. S. A. 106 (2009) 5264-5269
51. Broux, B. et al. (2010) Haplotype 4 of the multiple sclerosis-associated interleukin-7 receptor alpha gene influences the frequency of recent thymic emigrants. Genes Immun.doi:10.1038/gene.2009.106.
52. Mazzucchelli R., et al. Development of regulatory T cells requires IL-7Ralpha stimulation by IL-7 or TSLP. Blood 112 (2008) 3283-3292
53. Rosenkranz D., et al. Higher frequency of regulatory T cells in the elderly and increased suppressive activity in neurodegeneration. J. Neuroimmunol. 188 (2007) 117-127
54. Vukmanovic-Stejic M., et al. Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J. Clin. Invest. 116 (2006) 2423-2433
55. Feger U., et al. Increased frequency of CD4+ CD25+ regulatory T cells in the cerebrospinal fluid but not in the blood of multiple sclerosis patients. Clin. Exp. Immunol. 147 (2007) 412-418
56. McGeachy M.J., et al. Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system. J. Immunol. 175 (2005) 3025-3032
57. O'Connor R.A., et al. The inflamed central nervous system drives the activation and rapid proliferation of Foxp3+ regulatory T cells. J. Immunol. 179 (2007) 958-966
58. Korn T., et al. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat. Med. 13 (2007) 423-431
59. Korn T., et al. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 18460-18465
60. Stephens L.A., et al. Curing CNS autoimmune disease with myelin-reactive Foxp3+ Treg. Eur. J. Immunol. 39 (2009) 1108-1117
61. Hoffmann P., et al. Large scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells. Blood 104 (2004) 895-903
62. Battaglia M., et al. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J. Immunol. 177 (2006) 8338-8347
63. Riley J.L., et al. Human T regulatory cell therapy: take a billion or so and call me in the morning. Immunity 30 (2009) 656-665
64. Haas J., et al. Glatiramer acetate improves regulatory T-cell function by expansion of naive CD4(+)CD25(+)FOXP3(+)CD31(+) T-cells in patients with multiple sclerosis. J. Neuroimmunol. 216 (2009) 113-117
65. Korporal M., et al. Interferon beta-induced restoration of regulatory T-cell function in multiple sclerosis is prompted by an increase in newly generated naive regulatory T cells. Arch. Neurol. 65 (2008) 1434-1439
66. Platten M., et al. Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity. Proc. Natl. Acad. Sci. U. S. A. 106 (2009) 14948-14953
67. Smolders J., et al. Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PLoS One 4 (2009) e6635
68. Royal III W., et al. Peripheral blood regulatory T cell measurements correlate with serum vitamin D levels in patients with multiple sclerosis. J. Neuroimmunol. 213 (2009) 135-141
69. Zhou X., et al. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. 10 (2009) 1000-1007
70. Navarro J., et al. Circulating dendritic cells subsets and regulatory T-cells at multiple sclerosis relapse: differential short-term changes on corticosteroids therapy. J. Neuroimmunol. 176 (2006) 153-161
71. Xu L., et al. Glucocorticoid treatment restores the impaired suppressive function of regulatory T cells in patients with relapsing-remitting multiple sclerosis. Clin. Exp. Immunol. 158 (2009) 26-30
72. de Andres C., et al. Interferon beta-1a therapy enhances CD4+ regulatory T-cell function: an ex vivo and in vitro longitudinal study in relapsing-remitting multiple sclerosis. J. Neuroimmunol. 182 (2007) 204-211
73. Hong J., et al. Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 6449-6454
74. Stenner M.P., et al. Effects of natalizumab treatment on Foxp3+ T regulatory cells. PLoS One 3 (2008) e3319
75. Vandenbark A.A., et al. Therapeutic vaccination with a trivalent T-cell receptor (TCR) peptide vaccine restores deficient FoxP3 expression and TCR recognition in subjects with multiple sclerosis. Immunology 123 (2008) 66-78
76. Hong J., et al. CD4+ regulatory T cell responses induced by T cell vaccination in patients with multiple sclerosis. Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 5024-5029
77. Cox A.L., et al. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur. J. Immunol. 35 (2005) 3332-3342
78. Oh U., et al. Regulatory T cells are reduced during anti-CD25 antibody treatment of multiple sclerosis. Arch. Neurol. 66 (2009) 471-479
79. Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22 (2004) 531-562
80. Baecher-Allan C., et al. CD4+CD25high regulatory cells in human peripheral blood. J. Immunol. 167 (2001) 1245-1253
81. Roncador G., et al. Analysis of FOXP3 protein expression in human CD4(+)CD25(+) regulatory T cells at the single-cell level. Eur. J. Immunol. 35 (2005) 1681-1691
82. Bennett C.L., et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27 (2001) 20-21
83. Ziegler S.F. FOXP3: of mice and men. Annu. Rev. Immunol. 24 (2006) 209-226
84. Hori S., et al. Control of regulatory T cell development by the transcription factor Foxp3. Science 299 (2003) 1057-1061
85. Banham A.H., et al. FOXP3+ regulatory T cells: current controversies and future perspectives. Eur. J. Immunol. 36 (2006) 2832-2836
86. Allan S.E., et al. The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. J. Clin. Invest. 115 (2005) 3276-3284
87. Baron U., et al. DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. Eur. J. Immunol. 37 (2007) 2378-2389
88. Seddiki N., et al. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 203 (2006) 1693-1700
89. Shevach E.M. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 30 (2009) 636-645
90. Von Boehmer H. Mechanisms of suppression by suppressor T cells. Nat. Immunol. 6 (2005) 338-344
91. Miyara M., and Sakaguchi S. Natural regulatory T cells: mechanisms of suppression. Trends Mol. Med. 13 (2007) 108-116
92. Jordan M.S., et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2 (2001) 301-306
93. Spence P.J., and Green E.A. Foxp3+ regulatory T cells promiscuously accept thymic signals critical for their development. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 973-978
94. Wing K., et al. Characterization of human CD25+ CD4+ T cells in thymus, cord and adult blood. Immunology 106 (2002) 190-199
95. Seddiki N., et al. Persistence of naive CD45RA+ regulatory T cells in adult life. Blood 107 (2006) 2830-2838
96. Valmori D., et al. A peripheral circulating compartment of natural naive CD4 Tregs. J. Clin. Invest. 115 (2005) 1953-1962
97. Hazenberg M.D., et al. T cell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation. J. Mol. Med. 79 (2001) 631-640
98. Kimmig S., et al. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med. 195 (2002) 789-794
99. Fazilleau N., et al. Cutting edge: size and diversity of CD4+CD25high Foxp3+ regulatory T cell repertoire in humans: evidence for similarities and partial overlapping with CD4+. J. Immunol. 179 (2007) 3412-3416
100. Gregg R., et al. The number of human peripheral blood CD4+ CD25 high regulatory T cells increases with age. Clin. Exp. Immunol. 140 (2005) 540-546
101. Fisson S., et al. Continuous activation of autoreactive CD4+ CD25+ regulatory T cells in the steady state. J. Exp. Med. 198 (2003) 737-746
102. Matarese G., et al. Regulatory CD4 T cells: sensing the environment. Trends Immunol. 29 (2008) 12-17