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Regulatory T cells in human autoimmune diseases

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Abstract

In the most simplistic terms, immune tolerance can be envisioned as a balance with autoreactive cells that arise naturally in all individuals on one side and regulatory mechanisms designed to counter those autoreactive processes on the other. A tilt of the balance toward the autoreactive side, either by increasing the number or function of autoreactive cells or by diminishing regulatory mechanisms, is manifested as autoimmunity. In contrast, tilting of the balance toward increased regulation could conceivably cause immunodeficiency. Regulatory T cells (TREG), and particularly the naturally arising CD4+CD25+ subset of TREG cells, provide a substantial component of the autoimmune counterbalance. The identification of forkhead box P3 (FOXP3) as a critical determinant of CD4+CD25+ TREG development and function has provided new opportunities and generated expanded interest in studying the delicate balance between autoimmunity and regulatory mechanisms in human autoimmune diseases. Identification of both human and mouse syndromes in which FOXP3 is mutated, and consequently CD4+CD25+ TREG cells are absent, has led to a rapid accumulation of knowledge regarding TREG development and function over the past 5 years. The recent development of antibody reagents to specifically identify CD4+CD25+ TREG cells by their FOXP3 expression has provided new tools to identify these elusive cells and investigate their role in human disease. This review will focus on the current state of knowledge regarding the role of TREG in human autoimmune diseases and on specific human immunodeficiencies that provide interesting models of autoimmunity.

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Abbreviations

TREG :

Regulatory T cell

FOXP3:

Forkhead box P3

IL-2:

Interleukin 2

CTLA-4:

Cytotoxic T lymphocyte antigen-4

GITR:

Glucocorticoid-induced tumor necrosis factor receptor-related protein

References

  1. Agardh D, Lynch K, Brundin C et al (2006) Reduction of tissue transglutaminase autoantibody levels by gluten-free diet is associated with changes in subsets of peripheral blood lymphocytes in children with newly diagnosed coeliac disease. Clin Exp Immunol 144:67–75

    Article  PubMed  CAS  Google Scholar 

  2. Ahonen P, Myllarniemi S, Sipila I et al (1990) Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 322:1829–1836

    Article  PubMed  CAS  Google Scholar 

  3. Aleman K, Noordzij JG, de Groot R et al (2001) Reviewing Omenn syndrome. Eur J Pediatr 160:718–725

    PubMed  CAS  Google Scholar 

  4. Anderson MS, Venanzi ES, Klein L et al (2002) Projection of an immunological self shadow within the thymus by the aire protein. Science 298:1395–1401

    Article  PubMed  CAS  Google Scholar 

  5. Asano M, Toda M, Sakaguchi N et al (1996) Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med 184:387–396

    Article  PubMed  CAS  Google Scholar 

  6. Balandina A, Lecart S, Dartevelle P et al (2005) Functional defect of regulatory CD4+CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood 105:735–741

    Article  PubMed  CAS  Google Scholar 

  7. Battaglia A, Di Schino C, Fattorossi A et al (2005a) Circulating CD4+CD25+ T regulatory and natural killer T cells in patients with myasthenia gravis: a flow cytometry study. J Biol Regul Homeost Agents 19:54–62

    CAS  Google Scholar 

  8. Battaglia M, Stabilini A, Roncarolo MG (2005b) Rapamycin selectively expands CD4+CD25+FOXP3+ regulatory T cells. Blood 105(12):4743–4748

    Article  CAS  Google Scholar 

  9. Baud O, Goulet O, Canioni D et al (2001) Treatment of the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) by allogeneic bone marrow transplantation. N Engl J Med 344:1758–1762

    Article  PubMed  CAS  Google Scholar 

  10. Bennett CL, Brunkow ME, Ramsdell F et al (2001) A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA→AAUGAA) leads to the IPEX syndrome. Immunogenetics 53:435–439

    Article  PubMed  CAS  Google Scholar 

  11. Bennett CL, Christie J, Ramsdell F et al (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27:20–21

    Article  PubMed  CAS  Google Scholar 

  12. Betterle C, Greggio NA, Volpato M (1998) Clinical review 93: autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 83:1049–1055

    Article  PubMed  CAS  Google Scholar 

  13. Bindl L, Torgerson T, Perroni L et al (2005) Successful use of the new immune-suppressor sirolimus in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). J Pediatr 147:256–259

    Article  PubMed  Google Scholar 

  14. Bjorses P, Aaltonen J, Horelli-Kuitunen N et al (1998) Gene defect behind APECED: a new clue to autoimmunity. Hum Mol Genet 7:1547–1553

    Article  PubMed  CAS  Google Scholar 

  15. Bousvaros A, Leichtner AM, Book L et al (1996) Treatment of pediatric autoimmune enteropathy with tacrolimus (FK506). Gastroenterology 111:237–243

    Article  PubMed  CAS  Google Scholar 

  16. Boyer O, Saadoun D, Abriol J et al (2004) CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood 103:3428–3430

    Article  PubMed  CAS  Google Scholar 

  17. Brusko TM, Wasserfall CH, Clare-Salzler MJ et al (2005) Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes. Diabetes 54:1407–1414

    Article  PubMed  CAS  Google Scholar 

  18. Cavadini P, Vermi W, Facchetti F et al (2005) AIRE deficiency in thymus of 2 patients with Omenn syndrome. J Clin Invest 115:728–732

    PubMed  CAS  Google Scholar 

  19. Chatila TA (2005) Role of regulatory T cells in human diseases. J Allergy Clin Immunol 116:949–959

    Article  PubMed  CAS  Google Scholar 

  20. Chatila TA, Blaeser F, Ho N et al (2000) JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity–allergic disregulation syndrome. J Clin Invest 106:R75–R81

    Article  PubMed  CAS  Google Scholar 

  21. Coenen JJ, Koenen HJ, van Rijssen E et al (2006) Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells. Blood 107:1018–1023

    Article  PubMed  CAS  Google Scholar 

  22. Crispin JC, Martinez A, Alcocer-Varela J (2003) Quantification of regulatory T cells in patients with systemic lupus erythematosus. J Autoimmun 21:273–276

    Article  PubMed  Google Scholar 

  23. De Benedetti F, Insalaco A, Diamanti A et al (2006) Mechanistic associations of a mild phenotype of immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Clin Gastroenterol Hepatol 4:653–659

    Article  PubMed  CAS  Google Scholar 

  24. de Kleer IM, Wedderburn LR, Taams LS et al (2004) CD4+CD25(bright) regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol 172:6435–6443

    PubMed  Google Scholar 

  25. de Kleer I, Vastert B, Klein M et al (2006) Autologous stem cell transplantation for autoimmunity induces immunologic self-tolerance by reprogramming autoreactive T cells and restoring the CD4+CD25+ immune regulatory network. Blood 107:1696–1702

    Article  PubMed  CAS  Google Scholar 

  26. Drappa J, Vaishnaw AK, Sullivan KE et al (1996) Fas gene mutations in the Canale–Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. N Engl J Med 335:1643–1649

    Article  PubMed  CAS  Google Scholar 

  27. Dupuis-Girod S, Medioni J, Haddad E et al (2003) Autoimmunity in Wiskott–Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients. Pediatrics 111:e622–e627

    Article  PubMed  Google Scholar 

  28. Ege M, Ma Y, Manfras B et al (2005) Omenn syndrome due to ARTEMIS mutations. Blood 105:4179–4186

    Article  PubMed  CAS  Google Scholar 

  29. Fattorossi A, Battaglia A, Buzzonetti A et al (2005) Circulating and thymic CD4 CD25 T regulatory cells in myasthenia gravis: effect of immunosuppressive treatment. Immunology 116:134–141

    Article  PubMed  CAS  Google Scholar 

  30. Fisher GH, Rosenberg FJ, Straus SE et al (1995) Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 81:935–946

    Article  PubMed  CAS  Google Scholar 

  31. Fontenot JD, Rudensky AY (2005) A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 6:331–337

    Article  PubMed  CAS  Google Scholar 

  32. Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4:330–336

    Article  PubMed  CAS  Google Scholar 

  33. Fontenot JD, Rasmussen JP, Gavin MA et al (2005) A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 6:1142–1151

    Article  PubMed  CAS  Google Scholar 

  34. Furihata M, Sawada T, Okada T et al (2006) Total colectomy improves altered distribution of regulatory T cells in patients with ulcerative colitis. World J Surg 30:590–597

    Article  PubMed  Google Scholar 

  35. Furuno K, Yuge T, Kusuhara K et al (2004) CD25+CD4+ regulatory T cells in patients with Kawasaki disease. J Pediatr 145:385–390

    Article  PubMed  CAS  Google Scholar 

  36. Gambineri E, Torgerson TR, Ochs HD (2003) 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 15:430–435

    Article  PubMed  CAS  Google Scholar 

  37. Gavin MA, Torgerson TR, Houston E et al (2006) Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc Natl Acad Sci USA 103:6659–6664

    Article  PubMed  CAS  Google Scholar 

  38. Giannouli S, Anagnostou D, Soliotis F et al (2004) Autoimmune manifestations in common variable immunodeficiency. Clin Rheumatol 23:449–452

    Article  PubMed  Google Scholar 

  39. Giliani S, Bonfim C, de Saint Basile G et al (2006) Omenn syndrome in an infant with IL7RA gene mutation. J Pediatr 148:272–274

    Article  PubMed  CAS  Google Scholar 

  40. Haas J, Hug A, Viehover A et al (2005) Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur J Immunol 35:3343–3352

    Article  PubMed  CAS  Google Scholar 

  41. Heino M, Peterson P, Sillanpaa N et al (2000) RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur J Immunol 30:1884–1893

    Article  PubMed  CAS  Google Scholar 

  42. Hoglund P (2006) Induced peripheral regulatory T cells: the family grows larger. Eur J Immunol 36:264–266

    Article  PubMed  CAS  Google Scholar 

  43. Honig M, Schwarz K (2006) Omenn syndrome: a lack of tolerance on the background of deficient lymphocyte development and maturation. Curr Opin Rheumatol 18:383–388

    Article  PubMed  Google Scholar 

  44. Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061

    Article  PubMed  CAS  Google Scholar 

  45. Huan J, Culbertson N, Spencer L et al (2005) Decreased FOXP3 levels in multiple sclerosis patients. J Neurosci Res 81:45–52

    Article  PubMed  CAS  Google Scholar 

  46. Iellem A, Colantonio L, D’Ambrosio D (2003) Skin-versus gut-skewed homing receptor expression and intrinsic CCR4 expression on human peripheral blood CD4+CD25+ suppressor T cells. Eur J Immunol 33:1488–1496

    Article  PubMed  CAS  Google Scholar 

  47. Kalman L, Lindegren ML, Kobrynski L et al (2004) Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review. Genet Med 6:16–26

    Article  PubMed  CAS  Google Scholar 

  48. Kelsen J, Agnholt J, Hoffmann HJ et al (2005) FoxP3(+)CD4(+)CD25(+) T cells with regulatory properties can be cultured from colonic mucosa of patients with Crohn’s disease. Clin Exp Immunol 141:549–557

    Article  PubMed  CAS  Google Scholar 

  49. Khattri R, Cox T, Yasayko SA et al (2003) An essential role for scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 4:337–342

    Article  PubMed  CAS  Google Scholar 

  50. Kobayashi I, Nakanishi M, Okano M et al (1995) Combination therapy with tacrolimus and betamethasone for a patient with X-linked auto-immune enteropathy. Eur J Pediatr 154:594–595

    Article  PubMed  CAS  Google Scholar 

  51. Kriegel MA, Lohmann T, Gabler C et al (2004) Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J Exp Med 199:1285–1291

    Article  PubMed  CAS  Google Scholar 

  52. Lan RY, Cheng C, Lian ZX et al (2006) Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology 43:729–737

    Article  PubMed  Google Scholar 

  53. Lawson CA, Brown AK, Bejarano V et al (2006) Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood. Rheumatology (Oxford) DOI 10.1093/rheumatology/kel089

  54. Lee JH, Wang LC, Lin YT et al (2006) Inverse correlation between CD4+ regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus. Immunology 117:280–286

    Article  PubMed  CAS  Google Scholar 

  55. Lindley S, Dayan CM, Bishop A et al (2005) Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 54:92–99

    Article  PubMed  CAS  Google Scholar 

  56. Liston A, Lesage S, Wilson J et al (2003) Aire regulates negative selection of organ-specific T cells. Nat Immunol 4:350–354

    Article  PubMed  CAS  Google Scholar 

  57. Liu MF, Wang CR, Fung LL et al (2004) Decreased CD4+CD25+ T cells in peripheral blood of patients with systemic lupus erythematosus. Scand J Immunol 59:198–202

    Article  PubMed  Google Scholar 

  58. Liu MF, Wang CR, Fung LL et al (2005) The presence of cytokine-suppressive CD4+CD25+ T cells in the peripheral blood and synovial fluid of patients with rheumatoid arthritis. Scand J Immunol 62:312–317

    Article  PubMed  CAS  Google Scholar 

  59. Longhi MS, Ma Y, Bogdanos DP et al (2004) Impairment of CD4+CD25+ regulatory T-cells in autoimmune liver disease. J Hepatol 41:31–37

    Article  PubMed  CAS  Google Scholar 

  60. Longhi MS, Hussain MJ, Mitry RR et al (2006) Functional study of CD4+CD25+ regulatory T cells in health and autoimmune hepatitis. J Immunol 176:4484–4491

    PubMed  CAS  Google Scholar 

  61. Makita S, Kanai T, Oshima S et al (2004) CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells. J Immunol 173:3119–3130

    PubMed  CAS  Google Scholar 

  62. Mantel PY, Ouaked N, Ruckert B et al (2006) Molecular mechanisms underlying FOXP3 induction in human T cells. J Immunol 176:3593–3602

    PubMed  CAS  Google Scholar 

  63. Marinaki S, Neumann I, Kalsch AI et al (2005) Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis. Clin Exp Immunol 140:181–191

    Article  PubMed  CAS  Google Scholar 

  64. Maul J, Loddenkemper C, Mundt P et al (2005) Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology 128:1868–1878

    Article  PubMed  CAS  Google Scholar 

  65. Mazzolari E, Forino C, Fontana M et al (2005) A new case of IPEX receiving bone marrow transplantation. Bone Marrow Transplant 35:1033–1034

    Article  PubMed  CAS  Google Scholar 

  66. McGinness JL, Bivens MM, Greer KE et al (2006) Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) associated with pemphigoid nodularis: a case report and review of the literature. J Am Acad Dermatol 55:143–148

    Article  PubMed  Google Scholar 

  67. Miyara M, Amoura Z, Parizot C et al (2006) The immune paradox of sarcoidosis and regulatory T cells. J Exp Med 203:359–370

    Article  PubMed  Google Scholar 

  68. Möttönen M, Heikkinen J, Mustonen L et al (2005) 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 140:360–367

    Article  PubMed  Google Scholar 

  69. Nieves DS, Phipps RP, Pollock SJ et al (2004) Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Arch Dermatol 140:466–472

    Article  PubMed  Google Scholar 

  70. Ochs HD, Notarangelo LD (2005) Structure and function of the Wiskott–Aldrich syndrome protein. Curr Opin Hematol 12:284–291

    Article  PubMed  CAS  Google Scholar 

  71. Park O, Grishina I, Leung PS et al (2005) Analysis of the foxp3/scurfin gene in Crohn’s disease. Ann N Y Acad Sci 1051:218–228

    Article  PubMed  CAS  Google Scholar 

  72. Putnam AL, Vendrame F, Dotta F et al (2005) CD4+CD25high regulatory T cells in human autoimmune diabetes. J Autoimmun 24:55–62

    Article  PubMed  CAS  Google Scholar 

  73. Randolph DA, Fathman CG (2006) CD4+CD25+ regulatory T cells and their therapeutic potential. Annu Rev Med 57:381–402

    Article  PubMed  CAS  Google Scholar 

  74. Rieux-Laucat F, Le Deist F, Hivroz C et al (1995) Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 268:1347–1349

    Article  PubMed  CAS  Google Scholar 

  75. Rieux-Laucat F, Le Deist F, Fischer A (2003) Autoimmune lymphoproliferative syndromes: genetic defects of apoptosis pathways. Cell Death Differ 10:124–133

    Article  PubMed  CAS  Google Scholar 

  76. Roifman CM (2000) Human IL-2 receptor alpha chain deficiency. Pediatr Res 48:6–11

    Article  PubMed  CAS  Google Scholar 

  77. Roncador G, Brown PJ, Maestre L et al (2005) Analysis of FOXP3 protein expression in human CD4(+)CD25(+) regulatory T cells at the single-cell level. Eur J Immunol 35:1681–1691

    Article  PubMed  CAS  Google Scholar 

  78. Ruprecht CR, Gattorno M, Ferlito F et al (2005) Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia. J Exp Med 201:1793–1803

    Article  PubMed  CAS  Google Scholar 

  79. Ryan KR, Lawson CA, Lorenzi AR et al (2005) CD4+CD25+ T-regulatory cells are decreased in patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. J Allergy Clin Immunol 116:1158–1159

    Article  PubMed  CAS  Google Scholar 

  80. Sakaguchi S, Sakaguchi N, Asano M et al (1995) 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 155:1151–1164

    PubMed  CAS  Google Scholar 

  81. Schwartz RH (2005) Natural regulatory T cells and self-tolerance. Nat Immunol 6:327–330

    Article  PubMed  CAS  Google Scholar 

  82. Setoguchi R, Hori S, Takahashi T et al (2005) Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med 201:723–735

    Article  PubMed  CAS  Google Scholar 

  83. Sharfe N, Dadi HK, Shahar M et al (1997) Human immune disorder arising from mutation of the alpha chain of the interleukin-2 receptor. Proc Natl Acad Sci USA 94:3168–3171

    Article  PubMed  CAS  Google Scholar 

  84. Sun Y, Qiao J, Lu CZ et al (2004) Increase of circulating CD4+CD25+ T cells in myasthenia gravis patients with stability and thymectomy. Clin Immunol 112:284–289

    Article  PubMed  CAS  Google Scholar 

  85. Suri-Payer E, Amar AZ, Thornton AM et al (1998) CD4+CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. J Immunol 160:1212–1218

    PubMed  CAS  Google Scholar 

  86. Takahashi T, Kuniyasu Y, Toda M et al (1998) 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 10:1969–1980

    Article  PubMed  CAS  Google Scholar 

  87. Takahashi M, Nakamura K, Honda K et al (2006) An inverse correlation of human peripheral blood regulatory T cell frequency with the disease activity of ulcerative colitis. Dig Dis Sci 51:677–686

    Article  PubMed  Google Scholar 

  88. van Amelsfort JM, Jacobs KM, Bijlsma JW et al (2004) CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum 50:2775–2785

    Article  PubMed  Google Scholar 

  89. Venken K, Hellings N, Hensen K et al (2006) 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 83:1432–1446

    Article  PubMed  CAS  Google Scholar 

  90. Verhagen J, Akdis M, Traidl-Hoffmann C et al (2006) Absence of T-regulatory cell expression and function in atopic dermatitis skin. J Allergy Clin Immunol 117:176–183

    Article  PubMed  CAS  Google Scholar 

  91. Viglietta V, Baecher-Allan C, Weiner HL et al (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199:971–979

    Article  PubMed  CAS  Google Scholar 

  92. Vogel A, Strassburg CP, Obermayer-Straub P et al (2002) The genetic background of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and its autoimmune disease components. J Mol Med 80:201–211

    Article  PubMed  CAS  Google Scholar 

  93. Vukmanovic-Stejic M, McQuaid A, Birch KE et al (2005) Relative impact of CD4+CD25+ regulatory T cells and tacrolimus on inhibition of T-cell proliferation in patients with atopic dermatitis. Br J Dermatol 153:750–757

    Article  PubMed  CAS  Google Scholar 

  94. Walker MR, Kasprowicz DJ, Gersuk VH et al (2003) Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25− T cells. J Clin Invest 112:1437–1443

    PubMed  CAS  Google Scholar 

  95. Wildin RS, Freitas A (2005) IPEX and FOXP3: clinical and research perspectives. J Autoimmun 25(Suppl):56–62

    Article  PubMed  CAS  Google Scholar 

  96. Wildin RS, Ramsdell F, Peake J et al (2001) X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 27:18–20

    Article  PubMed  CAS  Google Scholar 

  97. Wildin RS, Smyk-Pearson S, Filipovich AH (2002) Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet 39:537–545

    Article  PubMed  CAS  Google Scholar 

  98. Willerford DM, Chen J, Ferry JA et al (1995) Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment. Immunity 3:521–530

    Article  PubMed  CAS  Google Scholar 

  99. Yagi H, Nomura T, Nakamura K et al (2004) Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol 16:1643–1656

    Article  PubMed  CAS  Google Scholar 

  100. Zlotogora J, Shapiro MS (1992) Polyglandular autoimmune syndrome type I among Iranian Jews. J Med Genet 29:824–826

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Pediatrics, Children’s Hospital and Regional Medical Center, University of Washington, 307 Westlake Ave. N., Suite 300, Seattle, WA, 98109, USA

    Troy R. Torgerson

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Torgerson, T.R. Regulatory T cells in human autoimmune diseases. Springer Semin Immun 28, 63–76 (2006). https://doi.org/10.1007/s00281-006-0041-4

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