Regulatory T cells and their role in rheumatic diseases: A potential target for novel therapeutic development

Pediatric Rheumatology

Volumn 6, Issue , 2008, Pages

  Milojevic, Diana ^a   Nguyen, Khoa D ^b   Wara, Diane ^a   Mellins, Elizabeth D ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b STANFORD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABATACEPT; CD45RA ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; INTERLEUKIN 1 ANTIBODY; INTERLEUKIN 15; INTERLEUKIN 2; INTERLEUKIN 6 ANTIBODY; INTERLEUKIN 7; LYMPHOCYTE ANTIBODY; RAPAMYCIN; RITUXIMAB; T LYMPHOCYTE RECEPTOR; THYMOCYTE ANTIBODY; TRANSCRIPTION FACTOR FOXP3; TUMOR NECROSIS FACTOR ALPHA ANTIBODY;

ANTIINFLAMMATORY ACTIVITY; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CD4+ CD25+ T LYMPHOCYTE; CYTOKINE PRODUCTION; CYTOTOXIC T LYMPHOCYTE; DRUG MEGADOSE; EFFECTOR CELL; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; IPEX SYNDROME; JUVENILE RHEUMATOID ARTHRITIS; LYMPHOCYTE FUNCTION; MUCOCUTANEOUS LYMPH NODE SYNDROME; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; RHEUMATIC DISEASE; RHEUMATOID ARTHRITIS; SARCOIDOSIS; SJOEGREN SYNDROME; SPONDYLOARTHROPATHY; SYSTEMIC LUPUS ERYTHEMATOSUS;

EID: 60649103594     PISSN: None     EISSN: 15460096     Source Type: Journal    
DOI: 10.1186/1546-0096-6-20     Document Type: Review

References (164)

1. Kappler JW Roehm N Marrack P T cell tolerance by clonal elimination in the thymus Cell 1987, 49:273-280. 3494522
2. Kisielow P Bluthmann H Staerz UD Steinmetz M von Boehmer H Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes Nature 1988, 333:742-746. 3260350
3. Anderson MS Venanzi ES Klein L Chen Z Berzins SP Turley SJ von Boehmer H Bronson R Dierich A Benoist C Mathis D Projection of an immunological self shadow within the thymus by the aire protein Science 2002, 298:1395-1401. 12376594
4. Villoslada P Abel K Heald N Goertsches R Hauser SL Genain CP Frequency, heterogeneity and encephalitogenicity of T cells specific for myelin oligodendrocyte glycoprotein in naive outbred primates Eur J Immunol 2001, 31:2942-2950. 11592070
5. Tiller T Tsuiji M Yurasov S Velinzon K Nussenzweig MC Wardemann H Autoreactivity in human IgG+ memory B cells Immunity 2007, 26:205-213. 1839941 17306569
6. Koelsch K Zheng NY Zhang Q Duty A Helms C Mathias MD Jared M Smith K Capra JD Wilson PC Mature B cells class switched to IgD are autoreactive in healthy individuals J Clin Invest 2007, 117:1558-1565. 1866247 17510706
7. Lohse AW Dinkelmann M Kimmig M Herkel J Meyer zum Buschenfelde KH Estimation of the frequency of self-reactive T cells in health and inflammatory diseases by limiting dilution analysis and single cell cloning J Autoimmun 1996, 9:667-675. 8933283
8. Fredrikson S Soderstrom M Hillert J Sun JB Kall TB Link H Multiple sclerosis: Occurrence of myelin basic protein peptide-reactive T cells in healthy family members Acta Neurol Scand 1994, 89:184-189. 7518178
9. Tada T Takemori T Selective roles of thymus-derived lymphocytes in the antibody response. I. Differential suppressive effect of carrier-primed T cells on hapten-specific IgM and IgG antibody responses J Exp Med 1974, 140:239-252. 2139696 4134784
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, 155:1151-1164. 7636184
11. Roncarolo MG Bacchetta R Bordignon C Narula S Levings MK Type 1 T regulatory cells Immunol Rev 2001, 182:68-79. 11722624
12. Levings MK Gregori S Tresoldi E Cazzaniga S Bonini C Roncarolo MG Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells Blood 2005, 105:1162-1169. 15479730
13. Cottrez F Groux H Specialization in tolerance: Innate CD(4+)CD(25+) versus acquired TR1 and TH3 regulatory T cells Transplantation 2004, 77:S12-15. 14726762
14. Weiner HL Oral tolerance: Immune mechanisms and the generation of Th3-type TGF-beta-secreting regulatory cells Microbes Infect 2001, 3:947-954. 11564443
15. Lan RY Ansari AA Lian ZX Gershwin ME Regulatory T cells: Development, function and role in autoimmunity Autoimmun Rev 2005, 4:351-363. 16081026
16. Weiner HL Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells Immunol Rev 2001, 182:207-214. 11722636
17. Zheng SG Gray JD Ohtsuka K Yamagiwa S Horwitz DA Generation ex vivo of TGF-beta-producing regulatory T cells from CD4+CD25- precursors J Immunol 2002, 169:4183-4189. 12370347
18. Seddon B Mason D The third function of the thymus Immunol Today 2000, 21:95-99. 10652468
19. Cupedo T Nagasawa M Weijer K Blom B Spits H Development and activation of regulatory T cells in the human fetus Eur J Immunol 2005, 35:383-390. 15682453
20. Yagi H Nomura T Nakamura K Yamazaki S Kitawaki T Hori S Maeda M Onodera M Uchiyama T Fujii S Sakaguchi S Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells Int Immunol 2004, 16:1643-1656. 15466453
21. Veldhoen M Hocking RJ Atkins CJ Locksley RM Stockinger B TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells Immunity 2006, 24:179-189. 16473830
22. Bensinger SJ Bandeira A Jordan MS Caton AJ Laufer TM Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4(+)25(+) immunoregulatory T cells J Exp Med 2001, 194:427-438. 2193499 11514600
23. Wing K Larsson P Sandstrom K Lundin SB Suri-Payer E Rudin A CD4+ CD25+ FOXP3+ regulatory T cells from human thymus and cord blood suppress antigen-specific T cell responses Immunology 2005, 115:516-525. 1782183 16011520
24. Sakaguchi S Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self Nat Immunol 2005, 6:345-352. 15785760
25. von Boehmer H Mechanisms of suppression by suppressor T cells Nat Immunol 2005, 6:338-344. 15785759
26. Picca CC Caton AJ The role of self-peptides in the development of CD4+ CD25+ regulatory T cells Curr Opin Immunol 2005, 17:131-136. 15766671
27. Fontenot JD Gavin MA Rudensky AY Foxp3 programs the development and function of CD4+CD25+ regulatory T cells Nat Immunol 2003, 4:330-336. 12612578
28. Hori S Nomura T Sakaguchi S Control of regulatory T cell development by the transcription factor Foxp3 Science 2003, 299:1057-1061. 12522256
29. Khattri R Cox T Yasayko SA Ramsdell F An essential role for Scurfin in CD4+CD25+ T regulatory cells Nat Immunol 2003, 4:337-342. 12612581
30. Hill JA Feuerer M Tash K Haxhinasto S Perez J Melamed R Mathis D Benoist C Foxp3 transcription-factor-dependent and - independent regulation of the regulatory T cell transcriptional signature Immunity 2007, 27:786-800. 18024188
31. Hsieh CS Liang Y Tyznik AJ Self SG Liggitt D Rudensky AY Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors Immunity 2004, 21:267-277. 15308106
32. Gavin MA Clarke SR Negrou E Gallegos A Rudensky A Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo Nat Immunol 2002, 3:33-41. 11740498
33. Fisson S Darrasse-Jeze G Litvinova E Septier F Klatzmann D Liblau R Salomon BL Continuous activation of autoreactive CD4+ CD25+ regulatory T cells in the steady state J Exp Med 2003, 198:737-746. 2194185 12939344
34. Allsopp RC Chang E Kashefi-Aazam M Rogaev EI Piatyszek MA Shay JW Harley CB Telomere shortening is associated with cell division in vitro and in vivo Exp Cell Res 1995, 220:194-200. 7664836
35. Pan C Xue BH Ellis TM Peace DJ Diaz MO Changes in telomerase activity and telomere length during human T lymphocyte senescence Exp Cell Res 1997, 231:346-353. 9087176
36. Gregg R Smith CM Clark FJ Dunnion D Khan N Chakraverty R Nayak L Moss PA The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age Clin Exp Immunol 2005, 140:540-546. 1809384 15932517
37. Mays LE Chen YH Maintaining immunological tolerance with Foxp3 Cell Res 2007, 17:904-918. 17923863
38. Chen W Jin W Hardegen N Lei KJ Li L Marinos N McGrady G Wahl SM Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3 J Exp Med 2003, 198:1875-1886. 2194145 14676299
39. Fantini MC Becker C Monteleone G Pallone F Galle PR Neurath MF Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7 J Immunol 2004, 172:5149-5153. 15100250
40. Peng Y Laouar Y Li MO Green EA Flavell RA TGF-beta regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes Proc Natl Acad Sci USA 2004, 101:4572-4577. 384788 15070759
41. Selvaraj RK Geiger TL A kinetic and dynamic analysis of Foxp3 induced in T cells by TGF-beta J Immunol 2007, 179:11. following 1390 17695668
42. Wang Z Hong J Sun W Xu G Li N Chen X Liu A Xu L Sun B Zhang JZ Role of IFN-gamma in induction of Foxp3 and conversion of CD4+ CD25- T cells to CD4+ Tregs J Clin Invest 2006, 116:2434-2441. 1533873 16906223
43. Walker MR Carson BD Nepom GT Ziegler SF Buckner JH De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25- cells Proc Natl Acad Sci USA 2005, 102:4103-4108. 554797 15753318
44. Walker MR Kasprowicz DJ Gersuk VH Benard A Van Landeghen M Buckner JH Ziegler SF Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells J Clin Invest 2003, 112:1437-1443. 228469 14597769
45. Skapenko A Kalden JR Lipsky PE Schulze-Koops H The IL-4 receptor alpha-chain-binding cytokines, IL-4 and IL-13, induce forkhead box P3-expressing CD25+CD4+ regulatory T cells from CD25-CD4+ precursors J Immunol 2005, 175:6107-6116. 16237107
46. Grimbert P Bouguermouh S Baba N Nakajima T Allakhverdi Z Braun D Saito H Rubio M Delespesse G Sarfati M Thrombospondin/CD47 interaction: A pathway to generate regulatory T cells from human CD4+ CD25- T cells in response to inflammation J Immunol 2006, 177:3534-3541. 16951312
47. Apostolou I von Boehmer H In vivo instruction of suppressor commitment in naive T cells J Exp Med 2004, 199:1401-1408. 2211808 15148338
48. Knoechel B Lohr J Kahn E Bluestone JA Abbas AK Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen J Exp Med 2005, 202:1375-1386. 2212975 16287710
49. Kretschmer K Apostolou I Hawiger D Khazaie K Nussenzweig MC von Boehmer H Inducing and expanding regulatory T cell populations by foreign antigen Nat Immunol 2005, 6:1219-1227. 16244650
50. Curotto de Lafaille MA Lino AC Kutchukhidze N Lafaille JJ CD25- T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansion J Immunol 2004, 173:7259-7268. 15585848
51. Thorstenson KM Khoruts A Generation of anergic and potentially immunoregulatory CD25+CD4 T cells in vivo after induction of peripheral tolerance with intravenous or oral antigen J Immunol 2001, 167:188-195. 11418648
52. Allan SE Passerini L Bacchetta R Crellin N Dai M Orban PC Ziegler SF Roncarolo MG Levings MK The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs J Clin Invest 2005, 115:3276-3284. 1242190 16211090
53. Gavin MA Torgerson TR Houston E DeRoos P Ho WY Stray-Pedersen A Ocheltree EL Greenberg PD Ochs HD Rudensky AY Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development Proc Natl Acad Sci USA 2006, 103:6659-6664. 1458937 16617117
54. Liu W Putnam AL Xu-Yu Z Szot GL Lee MR Zhu S Gottlieb PA Kapranov P Gingeras TR Fazekas de St Groth B Clayberger C Soper DM Ziegler SF Bluestone JA CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells J Exp Med 2006, 203:1701-1711. 2118339 16818678
55. Seddiki N Santner-Nanan B Martinson J Zaunders J Sasson S Landay A Solomon M Selby W Alexander SI Nanan R Kelleher A Fazekas de St Groth B Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells J Exp Med 2006, 203:1693-1700. 2118333 16818676
56. Zhang B Zhang X Tang FL Zhu LP Liu Y Lipsky PE Clinical significance of increased CD4+CD25-Foxp3+ T cells in patients with new-onset systemic lupus erythematosus Ann Rheum Dis 2008, 67:1037-1040. 18199598
57. Yi H Zhen Y Jiang L Zheng J Zhao Y The phenotypic characterization of naturally occurring regulatory CD4+CD25+ T cells Cell Mol Immunol 2006, 3:189-195. 16893499
58. Wei S Kryczek I Zou W Regulatory T-cell compartmentalization and trafficking Blood 2006, 108:426-431. 1895488 16537800
59. Curiel TJ Coukos G Zou L Alvarez X Cheng P Mottram P Evdemon-Hogan M Conejo-Garcia JR Zhang L Burow M Zhu Y Wei S Kryczek I Daniel B Gordon A Myers L Lackner A Disis ML Knutson KL Chen L Zou W Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival Nat Med 2004, 10:942-949. 15322536
60. Baecher-Allan C Brown JA Freeman GJ Hafler DA CD4+CD25high regulatory cells in human peripheral blood J Immunol 2001, 167:1245-1253. 11466340
61. Hamdy AF Bakr MA Ghoneim MA Long-term efficacy and safety of a calcineurin inhibitor-free regimen in live-donor renal transplant recipients J Am Soc Nephrol 2008, 19:1225-1232. 18337483
62. Zimmerman MA Trotter JF Wachs M Bak T Campsen J Skibba A Kam I Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma Liver Transpl 2008, 14:633-638. 18324656
63. Perez-Simon JA Sanchez-Abarca I Diez-Campelo M Caballero D San Miguel J Chronic graft-versus-host disease: Pathogenesis and clinical management Drugs 2006, 66:1041-1057. 16789791
64. Abraham RT Wiederrecht GJ Immunopharmacology of rapamycin Annu Rev Immunol 1996, 14:483-510. 8717522
65. Strauss L Whiteside TL Knights A Bergmann C Knuth A Zippelius A Selective survival of naturally occurring human CD4+CD25+Foxp3+ regulatory T cells cultured with rapamycin J Immunol 2007, 178:320-329. 17182569
66. Keever-Taylor CA Browning MB Johnson BD Truitt RL Bredeson CN Behn B Tsao A Rapamycin enriches for CD4(+) CD25(+) CD27(+) Foxp3(+) regulatory T cells in ex vivo-expanded CD25-enriched products from healthy donors and patients with multiple sclerosis Cytotherapy 2007, 9:144-157. 17453966
67. Turka LA Walsh PT IL-2 signaling and CD4+ CD25+ Foxp3+ regulatory T cells Front Biosci 2008, 13:1440-1446. 17981641
68. Hombach AA Kofler D Hombach A Rappl G Abken H Effective proliferation of human regulatory T cells requires a strong costimulatory CD28 signal that cannot be substituted by IL-2 J Immunol 2007, 179:7924-7931. 18025240
69. Oberg HH Wesch D Lenke J Kabelitz D An optimized method for the functional analysis of human regulatory T cells Scand J Immunol 2006, 64:353-360. 16918705
70. Ahn JS Krishnadas DK Agrawal B Dendritic cells partially abrogate the regulatory activity of CD4+CD25+ T cells present in the human peripheral blood Int Immunol 2007, 19:227-237. 17289657
71. Fehervari Z Sakaguchi S CD4+ Tregs and immune control J Clin Invest 2004, 114:1209-1217. 524236 15520849
72. Annunziato F Cosmi L Liotta F Lazzeri E Manetti R Vanini V Romagnani P Maggi E Romagnani S Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes J Exp Med 2002, 196:379-387. 2193942 12163566
73. Jonuleit H Schmitt E Kakirman H Stassen M Knop J Enk AH Infectious tolerance: Human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells J Exp Med 2002, 196:255-260. 2193929 12119350
74. Takahashi T Kuniyasu Y Toda M Sakaguchi N Itoh M Iwata M Shimizu J Sakaguchi S Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: Induction of autoimmune disease by breaking their anergic/suppressive state Int Immunol 1998, 10:1969-1980. 9885918
75. de la Rosa M Rutz S Dorninger H Scheffold A Interleukin-2 is essential for CD4+CD25+ regulatory T cell function Eur J Immunol 2004, 34:2480-2488. 15307180
76. Tang Q Boden EK Henriksen KJ Bour-Jordan H Bi M Bluestone JA Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function Eur J Immunol 2004, 34:2996-3005. 15468055
77. Read S Greenwald R Izcue A Robinson N Mandelbrot D Francisco L Sharpe AH Powrie F Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo J Immunol 2006, 177:4376-4383. 16982872
78. Paust S Lu L McCarty N Cantor H Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease Proc Natl Acad Sci USA 2004, 101:10398-10403. 478583 15235129
79. Chen W Jin W Wahl SM Engagement of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) induces transforming growth factor beta (TGF-beta) production by murine CD4(+) T cells J Exp Med 1998, 188:1849-1857. 2212416 9815262
80. Fallarino F Grohmann U Hwang KW Orabona C Vacca C Bianchi R Belladonna ML Fioretti MC Alegre ML Puccetti P Modulation of tryptophan catabolism by regulatory T cells Nat Immunol 2003, 4:1206-1212. 14578884
81. Stassen M Fondel S Bopp T Richter C Muller C Kubach J Becker C Knop J Enk AH Schmitt S Schmitt E Jonuleit H Human CD25+ regulatory T cells: two subsets defined by the integrins alpha 4 beta 7 or alpha 4 beta 1 confer distinct suppressive properties upon CD4+ T helper cells Eur J Immunol 2004, 34:1303-1311. 15114663
82. Raghavan S Suri-Payer E Holmgren J Antigen-specific in vitro suppression of murine Helicobacter pylori-reactive immunopathological T cells by CD4CD25 regulatory T cells Scand J Immunol 2004, 60:82-88. 15238076
83. Johnson BD Jing W Orentas RJ CD25+ regulatory T cell inhibition enhances vaccine-induced immunity to neuroblastoma J Immunother 2007, 30:203-214. 17471167
84. Xia G He J Zhang Z Leventhal JR Targeting acute allograft rejection by immunotherapy with ex vivo-expanded natural CD4+ CD25+ regulatory T cells Transplantation 2006, 82:1749-1755. 17198271
85. Cosmi L Liotta F Angeli R Mazzinghi B Santarlasci V Manetti R Lasagni L Vanini V Romagnani P Maggi E Annunziato F Romagnani S Th2 cells are less susceptible than Th1 cells to the suppressive activity of CD25+ regulatory thymocytes because of their responsiveness to different cytokines Blood 2004, 103:3117-3121. 15070693
86. Bopp T Palmetshofer A Serfling E Heib V Schmitt S Richter C Klein M Schild H Schmitt E Stassen M NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4+ T lymphocytes by CD4+ CD25+ regulatory T cells J Exp Med 2005, 201:181-187. 2212786 15657288
87. Suto A Nakajima H Kagami SI Suzuki K Saito Y Iwamoto I Role of CD4(+) CD25(+) regulatory T cells in T helper 2 cell-mediated allergic inflammation in the airways Am J Respir Crit Care Med 2001, 164:680-687. 11520737
88. Dieckmann D Bruett CH Ploettner H Lutz MB Schuler G Human CD4(+)CD25(+) regulatory, contact-dependent T cells induce interleukin 10-producing, contact-independent type 1-like regulatory T cells [corrected] J Exp Med 2002, 196:247-253. 2193931 12119349
89. Dieckmann D Plottner H Berchtold S Berger T Schuler G Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood J Exp Med 2001, 193:1303-1310. 2193384 11390437
90. Godfrey VL Wilkinson JE Russell LB X-linked lymphoreticular disease in the scurfy (sf) mutant mouse Am J Pathol 1991, 138:1379-1387. 1886400 2053595
91. Smyk-Pearson SK Bakke AC Held PK Wildin RS Rescue of the autoimmune scurfy mouse by partial bone marrow transplantation or by injection with T-enriched splenocytes Clin Exp Immunol 2003, 133:193-199. 1808763 12869024
92. Sullivan KE McDonald-McGinn D Zackai EH CD4(+) CD25(+) T-cell production in healthy humans and in patients with thymic hypoplasia Clin Diagn Lab Immunol 2002, 9:1129-1131. 120063 12204972
93. Itoh M Takahashi T Sakaguchi N Kuniyasu Y Shimizu J Otsuka F Sakaguchi S Thymus and autoimmunity: Production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance J Immunol 1999, 162:5317-5326. 10228007
94. Asano M Toda M Sakaguchi N Sakaguchi S Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation J Exp Med 1996, 184:387-396. 2192701 8760792
95. Gambineri E Torgerson 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, 15:430-435. 12819471
96. Bennett CL Christie J Ramsdell F Brunkow ME Ferguson PJ Whitesell L Kelly TE Saulsbury FT Chance PF Ochs HD The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3 Nat Genet 2001, 27:20-21. 11137993
97. Bacchetta R Passerini L Gambineri E Dai M Allan SE Perroni L Dagna-Bricarelli F Sartirana C Matthes-Martin S Lawitschka A Azzari C Ziegler SF Levings MK Roncarolo MG Defective regulatory and effector T cell functions in patients with FOXP3 mutations J Clin Invest 2006, 116:1713-1722. 1472239 16741580
98. Zhan H Sinclair J Adams S Cale CM Murch S Perroni L Davies G Amrolia P Qasim W Immune reconstitution and recovery of FOXP3 (forkhead box P3)-expressing T cells after transplantation for IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome Pediatrics 2008, 121:e998-1002. 18316354
99. Wildin RS Smyk-Pearson S Filipovich AH Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome J Med Genet 2002, 39:537-545. 1735203 12161590
100. Viglietta V Baecher-Allan C Weiner HL Hafler DA Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis J Exp Med 2004, 199:971-979. 2211881 15067033
101. Putnam AL Vendrame F Dotta F Gottlieb PA CD4+CD25high regulatory T cells in human autoimmune diabetes J Autoimmun 2005, 24:55-62. 15725577
102. Brusko T Atkinson M Treg in type 1 diabetes Cell Biochem Biophys 2007, 48:165-175. 17709886
103. Brusko T Wasserfall C McGrail K Schatz R Viener HL Schatz D Haller M Rockell J Gottlieb P Clare-Salzler M Atkinson M No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetes Diabetes 2007, 56:604-612. 17327427
104. Brusko TM Wasserfall CH Clare-Salzler MJ Schatz DA Atkinson MA Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes Diabetes 2005, 54:1407-1414. 15855327
105. Kukreja A Cost G Marker J Zhang C Sun Z Lin-Su K Ten S Sanz M Exley M Wilson B Porcelli S Maclaren N Multiple immuno-regulatory defects in type-1 diabetes J Clin Invest 2002, 109:131-140. 150819 11781358
106. de Kleer IM Wedderburn LR Taams LS Patel A Varsani H Klein M de Jager W Pugayung G Giannoni F Rijkers G Albani S Kuis W Prakken B CD4+CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis J Immunol 2004, 172:6435-6443. 15128835
107. Pasare C Medzhitov R Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells Science 2003, 299:1033-1036. 12532024
108. Cao D Malmstrom V Baecher-Allan C Hafler D Klareskog L Trollmo C Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis Eur J Immunol 2003, 33:215-223. 12594850
109. Massa M Passalia M Manzoni SM Campanelli R Ciardelli L Yung GP Kamphuis S Pistorio A Meli V Sette A Prakken B Martini A Albani S Differential recognition of heat-shock protein dnaJ-derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis Arthritis Rheum 2007, 56:1648-1657. 17469159
110. de Kleer I Vastert B Klein M Teklenburg G Arkesteijn G Yung GP Albani S Kuis W Wulffraat N Prakken B Autologous stem cell transplantation for autoimmunity induces immunologic self-tolerance by reprogramming autoreactive T cells and restoring the CD4+CD25+ immune regulatory network Blood 2006, 107:1696-1702. 16263787
111. Ruprecht CR Gattorno M Ferlito F Gregorio A Martini A Lanzavecchia A Sallusto F Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia J Exp Med 2005, 201:1793-1803. 2213274 15939793
112. Duggleby RC Shaw TN Jarvis LB Kaur G Gaston JS CD27 expression discriminates between regulatory and non-regulatory cells after expansion of human peripheral blood CD4+ CD25+ cells Immunology 2007, 121:129-139. 2265918 17425604
113. Liu MF Wang CR Fung LL Lin LH Tsai CN The presence of cytokine-suppressive CD4+CD25+ T cells in the peripheral blood and synovial fluid of patients with rheumatoid arthritis Scand J Immunol 2005, 62:312-317. 16179019
114. Cao D van Vollenhoven R Klareskog L Trollmo C Malmstrom V CD25brightCD4+ regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease Arthritis Res Ther 2004, 6:R335-346. 464877 15225369
115. Dombrecht EJ Aerts NE Schuerwegh AJ Hagendorens MM Ebo DG Van Offel JF Bridts CH Stevens WJ De Clerck LS Influence of anti-tumor necrosis factor therapy (Adalimumab) on regulatory T cells and dendritic cells in rheumatoid arthritis Clin Exp Rheumatol 2006, 24:31-37. 16539816
116. van Amelsfort JM Jacobs KM Bijlsma JW Lafeber FP Taams LS CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: Differences in the presence, phenotype, and function between peripheral blood and synovial fluid Arthritis Rheum 2004, 50:2775-2785. 15457445
117. Ehrenstein MR Evans JG Singh A Moore S Warnes G Isenberg DA Mauri C Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy J Exp Med 2004, 200:277-285. 2211983 15280421
118. Vigna-Perez M Abud-Mendoza C Portillo-Salazar H Alvarado-Sanchez B Cuevas-Orta E Moreno-Valdes R Baranda L Paredes-Saharopulos O Gonzalez-Amaro R Immune effects of therapy with Adalimumab in patients with rheumatoid arthritis Clin Exp Immunol 2005, 141:372-380. 1809428 15996202
119. Mottonen M Heikkinen J Mustonen L Isomaki P Luukkainen R Lassila O CD4+ CD25+ 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 2005, 140:360-367. 1809357 15807863
120. Jiao Z Wang W Jia R Li J You H Chen L Wang Y Accumulation of FoxP3-expressing CD4+CD25+ T cells with distinct chemokine receptors in synovial fluid of patients with active rheumatoid arthritis Scand J Rheumatol 2007, 36:428-433. 18092263
121. Behrens F Himsel A Rehart S Stanczyk J Beutel B Zimmermann SY Koehl U Moller B Gay S Kaltwasser JP Pfeilschifter JM Radeke HH Imbalance in distribution of functional autologous regulatory T cells in rheumatoid arthritis Ann Rheum Dis 2007, 66:1151-1156. 17392348
122. Wu HY Staines NA A deficiency of CD4+CD25+ T cells permits the development of spontaneous lupus-like disease in mice, and can be reversed by induction of mucosal tolerance to histone peptide autoantigen Lupus 2004, 13:192-200. 15119549
123. Rubio CF Kench J Russell DM Yawger R Nemazee D Analysis of central B cell tolerance in autoimmune-prone MRL/lpr mice bearing autoantibody transgenes J Immunol 1996, 157:65-71. 8683157
124. Fatenejad S Peng SL Disorbo O Craft J Central T cell tolerance in lupus-prone mice: Influence of autoimmune background and the lpr mutation J Immunol 1998, 161:6427-6432. 9834135
125. Crispin JC Martinez A Alcocer-Varela J Quantification of regulatory T cells in patients with systemic lupus erythematosus J Autoimmun 2003, 21:273-276. 14599852
126. Liu MF Wang CR Fung LL Wu CR Decreased CD4+CD25+ T cells in peripheral blood of patients with systemic lupus erythematosus Scand J Immunol 2004, 59:198-202. 14871297
127. Mellor-Pita S Citores MJ Castejon R Tutor-Ureta P Yebra-Bango M Andreu JL Vargas JA Decrease of regulatory T cells in patients with systemic lupus erythematosus Ann Rheum Dis 2006, 65:553-554. 16531555
128. Crispin JC Vargas MI Alcocer-Varela J Immunoregulatory T cells in autoimmunity Autoimmun Rev 2004, 3:45-51. 15003187
129. Azab NA Bassyouni IH Emad Y Abd El-Wahab GA Hamdy G Mashahit MA CD4+CD25+ regulatory T cells (TREG) in systemic lupus erythematosus (SLE) patients: The possible influence of treatment with corticosteroids Clin Immunol 2008, 127:151-157. 18299252
130. Lin SC Chen KH Lin CH Kuo CC Ling QD Chan CH The quantitative analysis of peripheral blood FOXP3-expressing T cells in systemic lupus erythematosus and rheumatoid arthritis patients Eur J Clin Invest 2007, 37:987-996. 18036033
131. Cepika AM Marinic I Morovic-Vergles J Soldo-Juresa D Gagro A Effect of steroids on the frequency of regulatory T cells and expression of FOXP3 in a patient with systemic lupus erythematosus: A two-year follow-up Lupus 2007, 16:374-377. 17576742
132. Valencia X Yarboro C Illei G Lipsky PE Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus J Immunol 2007, 178:2579-2588. 17277168
133. Lee JH Wang LC Lin YT Yang YH Lin DT Chiang BL Inverse correlation between CD4+ regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus Immunology 2006, 117:280-286. 1782210 16423064
134. Yan B Ye S Chen G Kuang M Shen N Chen S Dysfunctional CD4+, CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells Arthritis Rheum 2008, 58:801-812. 18311820
135. Barath S Soltesz P Kiss E Aleksza M Zeher M Szegedi G Sipka S The severity of systemic lupus erythematosus negatively correlates with the increasing number of CD4+CD25(high)FoxP3+ regulatory T cells during repeated plasmapheresis treatments of patients Autoimmunity 2007, 40:521-528. 17966042
136. Gottenberg JE Lavie F Abbed K Gasnault J Le Nevot E Delfraissy JF Taoufik Y Mariette X CD4 CD25high regulatory T cells are not impaired in patients with primary Sjogren's syndrome J Autoimmun 2005, 24:235-242. 15848046
137. Li X Li X Qian L Wang G Zhang H Wang X Chen K Zhai Z Li Q Wang Y Harris DC T regulatory cells are markedly diminished in diseased salivary glands of patients with primary Sjogren's syndrome J Rheumatol 2007, 34:2438-2445. 18050367
138. Furuno K Yuge T Kusuhara K Takada H Nishio H Khajoee V Ohno T Hara T CD25+CD4+ regulatory T cells in patients with Kawasaki disease J Pediatr 2004, 145:385-390. 15343196
139. Miyara M Amoura Z Parizot C Badoual C Dorgham K Trad S Kambouchner M Valeyre D Chapelon-Abric C Debre P Piette JC Gorochov G The immune paradox of sarcoidosis and regulatory T cells J Exp Med 2006, 203:359-370. 2118208 16432251
140. Idali F Wahlstrom J Muller-Suur C Eklund A Grunewald J Analysis of regulatory T cell associated forkhead box P3 expression in the lungs of patients with sarcoidosis Clin Exp Immunol 2008, 152:127-137. 18279440
141. Brusko TM Putnam AL Bluestone JA Human regulatory T cells: Role in autoimmune disease and therapeutic opportunities Immunol Rev 2008, 223:371-390. 18613848
142. Mudd PA Teague BN Farris AD Regulatory T cells and systemic lupus erythematosus Scand J Immunol 2006, 64:211-218. 16918689
143. O'Sullivan BJ Thomas HE Pai S Santamaria P Iwakura Y Steptoe RJ Kay TW Thomas R IL-1 beta breaks tolerance through expansion of CD25+ effector T cells J Immunol 2006, 176:7278-7287. 16751371
144. Wan S Xia C Morel L IL-6 produced by dendritic cells from lupus-prone mice inhibits CD4+CD25+ T cell regulatory functions J Immunol 2007, 178:271-279. 17182564
145. Stoop JN Woltman AM Biesta PJ Kusters JG Kuipers EJ Janssen HL Molen van der RG Tumor necrosis factor alpha inhibits the suppressive effect of regulatory T cells on the hepatitis B virus-specific immune response Hepatology 2007, 46:699-705. 17654744
146. Hasegawa H Inoue A Muraoka M Yamanouchi J Miyazaki T Yasukawa M Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4+ CD25+ regulatory T cells in MRL/lpr mice Arthritis Res Ther 2007, 9:R15. 1860074 17284325
147. Yang L Anderson DE Baecher-Allan C Hastings WD Bettelli E Oukka M Kuchroo VK Hafler DA IL-21 and TGF-beta are required for differentiation of human T(H)17 cells Nature 2008, 454:350-352. 18469800
148. Liu H Hu B Xu D Liew FY CD4+CD25+ regulatory T cells cure murine colitis: The role of IL-10, TGF-beta, and CTLA4 J Immunol 2003, 171:5012-5017. 14607897
149. Kohm AP Carpentier PA Anger HA Miller SD 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 2002, 169:4712-4716. 12391178
150. Tarbell KV Yamazaki S Olson K Toy P Steinman RM CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes J Exp Med 2004, 199:1467-1477. 2211787 15184500
151. Nagahama K Nishimura E Sakaguchi S Induction of tolerance by adoptive transfer of Treg cells Methods Mol Biol 2007, 380:431-442. 17876110
152. Nishimura E Sakihama T Setoguchi R Tanaka K Sakaguchi S Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells Int Immunol 2004, 16:1189-1201. 15237110
153. Noris M Casiraghi F Todeschini M Cravedi P Cugini D Monteferrante G Aiello S Cassis L Gotti E Gaspari F Cattaneo D Perico N Remuzzi G Regulatory T cells and T cell depletion: Role of immunosuppressive drugs J Am Soc Nephrol 2007, 18:1007-1018. 17287424
154. Minamimura K Gao W Maki T CD4+ regulatory T cells are spared from deletion by antilymphocyte serum, a polyclonal anti-T cell antibody J Immunol 2006, 176:4125-4132. 16547248
155. Lopez M Clarkson MR Albin M Sayegh MH Najafian N A novel mechanism of action for anti-thymocyte globulin: Induction of CD4+CD25+Foxp3+ regulatory T cells J Am Soc Nephrol 2006, 17:2844-2853. 16914538
156. Yates J Rovis F Mitchell P Afzali B Tsang JY Garin M Lechler RI Lombardi G Garden OA The maintenance of human CD4+ CD25+ regulatory T cell function: IL-2, IL-4, IL-7 and IL-15 preserve optimal suppressive potency in vitro Int Immunol 2007, 19:785-799. 17545278
157. Imamichi H Sereti I Lane HC IL-15 acts as a potent inducer of CD4(+ )CD25(hi) cells expressing FOXP3 Eur J Immunol 2008, 38:1621-1630. 18493981
158. Niedbala W Wei XQ Cai B Hueber AJ Leung BP McInnes IB Liew FY IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells Eur J Immunol 2007, 37:3021-3029. 17874423
159. Korn T Bettelli E Gao W Awasthi A Jager A Strom TB Oukka M Kuchroo VK IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells Nature 2007, 448:484-487. 17581588
160. Karandikar NJ Vanderlugt CL Walunas TL Miller SD Bluestone JA CTLA-4: A negative regulator of autoimmune disease J Exp Med 1996, 184:783-788. 2192746 8760834
161. Bluestone JA Thomson AW Shevach EM Weiner HL What does the future hold for cell-based tolerogenic therapy? Nat Rev Immunol 2007, 7:650-654. 17653127
162. Barrett AJ Manipulating regulatory T cells Cytotherapy 2007, 9:109-110. 17453962
163. Battaglia M Stabilini A Migliavacca B Horejs-Hoeck J Kaupper T Roncarolo MG Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients J Immunol 2006, 177:8338-8347. 17142730
164. Horibe EK Sacks J Unadkat J Raimondi G Wang Z Ikeguchi R Marsteller D Ferreira LM Thomson AW Lee WP Feili-Hariri M Rapamycin-conditioned, alloantigen-pulsed dendritic cells promote indefinite survival of vascularized skin allografts in association with T regulatory cell expansion Transpl Immunol 2008, 18:307-318. 18158116