Foxp3 Expressing Regulatory T-Cells in Allergic Disease

  • Kayhan T. Nouri-AriaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 665)


Allergic diseases such as asthma, rhinitis and eczema are increasing in prevalence worldwide, in particular in industrialised countries affecting up to 20% of the population. Regulatory T-cells (Tregs) have been shown to be critical in T-cell homeostasis and in the maintenance of immune responses, such as prevention of autoimmunity and hampering allergic diseases. The so-called ‘natural’ CD4+CD25+ Tregs and/or IL-10-producing Tr1 cells have been shown to be responsible for the protection of immune tolerance and intact immune reactions following exposure to allergens such as aeroallergens or food allergens. In this regard, both cell-cell contact (through membrane bound TGF-β or via suppressive molecules such as CLTA-4) and soluble cytokine-(TGF-β and IL-10) dependent mechanisms have been shown to contribute to the ability of Tregs to operate effectively. The transcription factor Foxp3, a member of the forkhead-winged helix family, appears to be critical in the suppressive abilities of regulatory T-cells. Adoptive transfer of CD4+CD25+ Tregs from healthy to diseased animals corroborated and provided further evidence of the vital role of these populations in the prevention or cure of certain autoimmune conditions. Clinical improvement seen after allergen immunotherapy for allergic diseases such as rhinitis and asthma has also been associated with the induction of IL-10 and TGF-β producing Tr1 cells as well as Foxp3 expressing CD4+CD25+ T-cells, resulting in the suppression of Th2 cytokine milieu. Activation and expansion of antigen-specific CD4+CD25+ Tregs in vivo using adjuvants such as IL-10 or pharmacological agents such as low dose steroids or vitamin D3 could represent novel approaches to induce antigen-specific tolerance in immune-mediated conditions such as allergic asthma, autoimmune disease and the rejection of transplanted organs in man.


Atopic Dermatitis Treg Cell Allergic Rhinitis Allergic Disease Allergy Clin Immunol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Sakaguchi S, Sakaguchi N, Asano M 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 1995; 155:1151–1164.PubMedGoogle Scholar
  2. 2.
    Asano M, Toda M, Sakaguchi N et al. Autoimmune disease as a consequence of developmental abnormality of a T-cell subpopulation. J Exp Med 1996; 184:387–396.CrossRefPubMedGoogle Scholar
  3. 3.
    Ng WF, Duggan PJ, Ponchel F et al. Human CD4+CD25+ cells: a naturally occurring population of regulatory T-cells. Blood 2001; 98:2736–2744.CrossRefPubMedGoogle Scholar
  4. 4.
    Jonuleit H, Schmitt E, Stassen M et al. Identification and functional characterization of human CD4+CD25+ T-cells with regulatory properties isolated from peripheral blood. J Exp Med 2001; 193:1285–1294.CrossRefPubMedGoogle Scholar
  5. 5.
    Dieckmann D, Plottner H, Berchtold S et al. Ex vivo isolation and characterization of CD4+CD25+ T-cells with regulatory properties from human blood. J Exp Med 2001; 193:1303–1310.CrossRefPubMedGoogle Scholar
  6. 6.
    Levings MK, Sangregorio R, Roncarolo MG. Human CD25+CD4+ T regulatory cells suppress naive and memory T-cell proliferation and can be expanded in vitro without loss of function. J Exp Med 2001; 193:1295–1302.CrossRefPubMedGoogle Scholar
  7. 7.
    Thornton AM, Shevach EM. CD4+CD25+ immunoregulatory T-cells suppress polyclonal T-cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 1998; 188:287–296.CrossRefPubMedGoogle Scholar
  8. 8.
    Bayer AL, Yu A, Adeegbe D et al. Essential role for interleukin-2 for CD4+CD25+ T regulatory cell development during the neonatal period. J Exp Med 2005; 201:769–777.CrossRefPubMedGoogle Scholar
  9. 9.
    Read S, Malmstrom V, Powrie F. Cytotoxic T-lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J Exp Med 2000; 19:295–302.CrossRefGoogle Scholar
  10. 10.
    Graca L, Honey K, Adams E et al. Cutting edge: anti-CD 154 therapeutic antibodies induce infectious transplantation tolerance. J Immunol 2000; 165:4783–4786.PubMedGoogle Scholar
  11. 11.
    McHugh RS, Whitters MJ, Piccirillo CA et al. CD4+CD25+ immunoregulatory T-cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002; 1:311–323.CrossRefGoogle Scholar
  12. 12.
    Liu W, Putnam AL, Xu-Yu Z et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ Treg cells. J Exp Med 2006; 203:1701–1711.CrossRefPubMedGoogle Scholar
  13. 13.
    Nouri-Aria KT, Durham SR. Regulatory T-cells and allergic disease. Inflamm Allergy Drug Targets 2008; 7:237–52. Review.CrossRefPubMedGoogle Scholar
  14. 14.
    Hori S, Nomura T, Sakaguchi S. Control of regulatory T-cell development by the transcription factor Foxp3. Science 2003; 299:1057–1061.CrossRefPubMedGoogle Scholar
  15. 15.
    Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T-cells. Nat Immunol 2003; 4:330–336.CrossRefPubMedGoogle Scholar
  16. 16.
    Brandenburg S, Takahashi T, de la Rosa M et al. IL-2 induces in vivo suppression by CD4+CD25+Foxp3+ regulatory T-cells. Eur J Immunol 2008; 38:1643–1653.CrossRefPubMedGoogle Scholar
  17. 17.
    Lin W, Haribhai D, Relland LM et al. Regulatory T-cell development in the absence of functional Foxp3. Nat Immunol 2007; 8:359–368.CrossRefPubMedGoogle Scholar
  18. 18.
    Khattri R, Cox T, Yasayko SA et al. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003; 4:337–342.CrossRefPubMedGoogle Scholar
  19. 19.
    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.CrossRefPubMedGoogle Scholar
  20. 20.
    Yagi H, Nomura T, Nakamura K et al. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T. Int Immunol 2004; 16:1643–1656.CrossRefPubMedGoogle Scholar
  21. 21.
    Ziegler SF. FOXP3: of mice and men. Annu Rev Immunol 2006; 24:209–226. Review.CrossRefPubMedGoogle Scholar
  22. 22.
    Schmidt-Weber CB, Blaser K. The role of the FOXP3 transcription factor in the immune regulation of allergic asthma. Curr Allergy Asthma Rep 2005; 5:356–361.CrossRefPubMedGoogle Scholar
  23. 23.
    Mantel PY, Ouaked N, Ruckert B et al. Molecular mechanisms underlying FOXP3 induction in human T-cells. J Immunol 2006; 176:3593–3602.PubMedGoogle Scholar
  24. 24.
    Zorn E, Nelson EA, Mohseni M et al. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T-cells through a STAT dependent mechanism and induces the expansion of these cells in vivo. Blood 2006; 108:1571–1579.CrossRefPubMedGoogle Scholar
  25. 25.
    Fontenot JD, Rasmussen JP, Gavin MA et al. A function for interleukin 2 in Foxp3-expressing regulatory T-cells. Nat Immunol 2005; 6:1142–1151.CrossRefPubMedGoogle Scholar
  26. 26.
    Janson PC, Winerdal ME, Marits P et al. FOXP3 promoter demethylation reveals the committed Treg population in humans. PLoS ONE 2008; 3:e1612.CrossRefPubMedGoogle Scholar
  27. 27.
    Allan SE, Song-Zhao GX, Abraham T et al. Inducible reprogramming of human T-cells into Treg cells by a conditionally active form of FOXP3. Eur J Immunol 2008; 38:3282–3289.CrossRefPubMedGoogle Scholar
  28. 28.
    Bardel E, Larousserie F, Charlot-Rabiega P. Human CD4+CD25+Foxp3+ regulatory T-cells do not constitutively express IL-35. J Immunol 2008; 181:6898–6905.PubMedGoogle Scholar
  29. 29.
    Collison LW, Workman CJ, Kuo TT et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007; 450:566–569.CrossRefPubMedGoogle Scholar
  30. 30.
    Cottrez F, Hurst SD, Coffman RL et al. T regulatory cells 1 inhibit a Th2-specific response in vivo. J Immunol 2000; 165:4848–4853.PubMedGoogle Scholar
  31. 31.
    Akdis M, Verhagen J, Taylor A et al. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 2004; 199:1567–1575.CrossRefPubMedGoogle Scholar
  32. 32.
    Ling EM, Smith T, Dao Nguyen X et al. Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 2004; 363:608–615.CrossRefPubMedGoogle Scholar
  33. 33.
    Karlsson MR, Rugtveit J, Brandtzaeg P. Allergen-responsive CD4+CD25+ regulatory T-cells in children who have outgrown cow’s milk allergy. J Exp Med 2004; 199:1679–1688.CrossRefPubMedGoogle Scholar
  34. 34.
    Akdis M, Blaser K, Akdis CA. T regulatory cells in allergy. Chem Immunol Allergy 2006; 91:159–173. Review.CrossRefPubMedGoogle Scholar
  35. 35.
    Sumi T, Fukushima A, Fukuda K et al. Thymus-derived CD4+ CD25+ T-cells suppress the development of murine allergic conjunctivitis. Int Arch Allergy Immunol 2007; 143:276–81.CrossRefPubMedGoogle Scholar
  36. 36.
    Lin W, Truong N, Grossman WJ et al. Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice. J Allergy Clin Immunol 2005; 116:1106–15.CrossRefPubMedGoogle Scholar
  37. 37.
    Van Hove CL, Maes T, Joos GF et al. Prolonged inhaled allergen exposure can induce persistent tolerance. Am J Respir Cell Mol Biol 2007; 36:573–84.CrossRefPubMedGoogle Scholar
  38. 38.
    Borish L. IL-10: evolving concepts. J Allergy Cli Immunol 1998; 101:293–297.CrossRefGoogle Scholar
  39. 39.
    Scherf W, Burdach S, Hansen G. Reduced expression of transforming growth factor beta 1 exacerbates pathology in an experimental asthma model. Eur J Immunol 2005; 35:198–206.CrossRefPubMedGoogle Scholar
  40. 40.
    Frossard CP, Hauser C, Eigenmann PA. Antigen-specificsecretory IgA antibodies in the gut are decreased in a mouse model of food allergy. J Allergy Clin Immunol 2004; 114:377–382.CrossRefPubMedGoogle Scholar
  41. 41.
    Burchell JT, Wikstrom ME, Stumbles PA et al. Attenuation of allergen-induced Airway Hyperresponsiveness is mediated by airway regulatory T-cells. Am J Physiol Lung Cell Mol Physiol 2008. (Epub ahead of print)Google Scholar
  42. 42.
    Carson WF 4th, Guernsey LA, Singh A et al. Accumulation of regulatory T-cells in local draining lymph nodes of the lung correlates with spontaneous resolution of chronic asthma in a murine model. Int Arch Allergy Immunol 2008; 145:231–43.CrossRefPubMedGoogle Scholar
  43. 43.
    Ostroukhova M, Seguin-Devaux C, Oriss TB et al. Tolerance induced by inhaled antigen involves CD4+ T-cells expressing membrane-bound TGF-beta and FOXP3. J Clin Invest 2004; 114:28–38.PubMedGoogle Scholar
  44. 44.
    Stock P, DeKruyff RH, Umetsu DT. Inhibition of the allergic response by regulatory T-cells. Curr Opin Allergy Clin Immunol 2006; 6:12–6. Review.CrossRefPubMedGoogle Scholar
  45. 45.
    Francis JN, Till SJ, Durham SR. Induction of IL-10+CD4+CD25+ T-cells by grass pollen immunotherapy. J Allergy Clin Immunol 2003; 111:1255–1261.CrossRefPubMedGoogle Scholar
  46. 46.
    Grindebacke H, Wing K, Andersson AC et al. Defective suppression of Th2 cytokines by CD4CD25 regulatory T-cells in birch allergies during birch pollen season. Clin Exp Allergy 2004; 3:1364–1372.CrossRefGoogle Scholar
  47. 47.
    Xu G, Mou Z, Jiang H et al. A possible role of CD4+CD25+ T-cells as well as transcription factor Foxp3 in the dysregulation of allergic rhinitis. Laryngoscope 2007; 117:876–80.CrossRefPubMedGoogle Scholar
  48. 48.
    Lee JH, Yu HH, Wang LC et al. The levels of CD4+CD25+ regulatory T-cells in paediatric patients with allergic rhinitis and bronchial asthma. Clin Exp Immunol 2007; 148:53–63.PubMedGoogle Scholar
  49. 49.
    Thunberg S, Akdis M, Akdis CA et al. Immune regulation by CD4+CD25+ T-cells and interleukin-10 in birch pollen-allergic patients and non-allergic controls. Clin Exp Allergy 2007; 37:1127–1136.CrossRefPubMedGoogle Scholar
  50. 50.
    Maggi L, Santarlasci V, Liotta F et al. Demonstration of circulating allergen-specific CD4+CD25highFoxp3+ T-regulatory cells in both nonatopic and atopic individuals. J Allergy Clin Immunol 2007; 120:429–436.CrossRefPubMedGoogle Scholar
  51. 51.
    Nagato T, Kobayashi H, Yanai M et al. Functional analysis of birch pollen allergen Bet v 1-specific regulatory T-cells. J Immunol 2007; 178:1189–1198.PubMedGoogle Scholar
  52. 52.
    Winkler B, Hufnagl K, Spittler A et al. The role of Foxp3+ T-cells in long-term efficacy of prophylactic and therapeutic mucosal tolerance induction in mice. Allergy 2006; 61:173–80.CrossRefPubMedGoogle Scholar
  53. 53.
    Wilson MS, Taylor MD, Balic A et al. Suppression of allergic airway inflammation by helminth-induced regulatory T-cells. J Exp Med 2005; 202:1199–212.CrossRefPubMedGoogle Scholar
  54. 54.
    Flohr C, Quinnell RJ, Britton J. Do helminth parasites protect against atopy and allergic disease? Clin Exp Allergy 2009; 39:20–32.CrossRefPubMedGoogle Scholar
  55. 55.
    Schaub B, Liu J, Höppler S et al. Impairment of T-regulatory cells in cord blood of atopic mothers. J Allergy Clin Immunol 2008; 121:1491–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Smith M, Tourigny MR, Noakes P et al. Children with egg allergy have evidence of reduced neonatal CD4+CD25+CD127lo/− regulatory T-cell function. J Allergy Clin Immunol 2008; 121:1460–6.CrossRefPubMedGoogle Scholar
  57. 57.
    Schaub B, Campo M, He H et al. Neonatal immune responses to TLR2 stimulation: influence of maternal atopy on Foxp3 and IL-10 expression. Respir Res 2006; 21:7:40–48.Google Scholar
  58. 58.
    Reefer AJ, Satinover SM, Solga MD et al. Analysis of CD25hiCD4+ “regulatory” T-cell subtypes in atopic dermatitis reveals a novel TH2-like population. J Allergy Clin Immunol 2008; 121:415–422.CrossRefPubMedGoogle Scholar
  59. 59.
    Caproni M, Antiga E, Torchia D et al. FoxP3-expressing T regulatory cells in atopic dermatitis lesions. Allergy Asthma Proc 2007; 28:525–528.CrossRefPubMedGoogle Scholar
  60. 60.
    de Boer OJ, van der Loos CM, Teeling P et al. Immunohistochemical analysis of regulatory T-cell markers FOXP3 and GITR on CD4+CD25+ T-cells in normal skin and inflammatory dermatoses. J Histochem Cytochem 2007; 55:891–898.CrossRefPubMedGoogle Scholar
  61. 61.
    O’Garra A, Barrat FJ, Castro AG et al. Strategies for use of IL-10 or its antagonists in human disease. Immunol Rev 2008; 223:114–131.CrossRefPubMedGoogle Scholar
  62. 62.
    Xystrakis E, Kusumakar S, Boswell S et al. Reversing the defective induction of IL-10-secreting regulatory T-cells in glucocorticoid-resistant asthma patients. J Clin Invest 2006; 116:146–155.CrossRefPubMedGoogle Scholar
  63. 63.
    Hartl D, Koller B, Mehlhorn AT et al. Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T-cells in pediatric asthma. J Allergy Clin Immunol 2007; 119:1258–66.CrossRefPubMedGoogle Scholar
  64. 64.
    Durham SR. Allergen immunotherapy (desensitisation) for allergic diseases. Clin Med 2006; 6:348–351.PubMedGoogle Scholar
  65. 65.
    Nelson HS. Advances in upper airway diseases and allergen immunotherapy. J Allergy Clin Immunol 2007; 119:872–880.CrossRefPubMedGoogle Scholar
  66. 66.
    Noon L. Prophylactic inoculation against hay fever. Lancet 1911; 1:1572–1573.CrossRefGoogle Scholar
  67. 67.
    Frew AJ, Powell RJ, Corrigan CJ et al. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 117:319–325.CrossRefPubMedGoogle Scholar
  68. 68.
    Walker SM, Pajno GB, Lima MT et al. Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial. J Allergy Clin Immunol 2001; 107:87–93.CrossRefPubMedGoogle Scholar
  69. 69.
    Akdis CA, Blesken T, Akdis M et al. Role of interleukin 10 in specific immunotherapy. J Clin Invest 1998; 102:98–106.CrossRefPubMedGoogle Scholar
  70. 70.
    Durham SR, Walker SM, Varga EM et al. Long-Term Clinical Efficacy of Grass-Pollen Immunotherapy. New Engl J Med 1999; 341:468–475.CrossRefPubMedGoogle Scholar
  71. 71.
    Wachholz PA, Nouri-Aria KT, Wilson DR et al. Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1:Th2 cytokine ratios. Immunology 2002; 105:56–62.CrossRefPubMedGoogle Scholar
  72. 72.
    Till SJ, Francis JN, Nouri-Aria K et al. Mechanisms of immunotherapy. J Allergy Clin Immunol 2004; 113:1025–1034. Review.CrossRefPubMedGoogle Scholar
  73. 73.
    Robinson DS, Larche M, Durham SR. Tregs and allergic disease. J Clin Invest 2004; 114:1389–1397. Review.PubMedGoogle Scholar
  74. 74.
    Verhagen J, Taylor A, Blaser K et al. T regulatory cells in allergen-specific immunotherapy. Int Rev Immunol 2005; 24:533–548. Review.CrossRefPubMedGoogle Scholar
  75. 75.
    Ajduk J, Marinic I, Aberle N et al. Effect of house dust mite immunotherapy on transforming growth factor betal-producing T-cells in asthmatic children. Ann Allergy Asthma Immunol 2008; 100:314–22.CrossRefPubMedGoogle Scholar
  76. 76.
    Mekala DJ, Alli RS, Geiger TL. IL-10-dependent infectious tolerance after the treatment of experimental allergic encephalomyelitis with redirected CD4+CD25+ T-Iymphocytes. Proc Natl Acad Sci USA 2005; 102:11817–11822.CrossRefPubMedGoogle Scholar
  77. 77.
    Akdis CA, Joss A, Akdis M et al. A molecular basis for T-cell suppression by IL-10: CD28-associated IL-10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3-kinase binding. FASEB J 2000; 14:1666–1668.PubMedGoogle Scholar
  78. 78.
    Nouri-Aria KT, Wachholz PA, Francis JN et al. Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol 2004; 172:3252–3259.PubMedGoogle Scholar
  79. 79.
    Pilette C, Nouri-Aria KT, Jacobson MR et al. Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression. J Immunol 2007; 178:4658–4666.PubMedGoogle Scholar
  80. 80.
    Jutel M, Akdis M, Budak F et al. IL-10 and TGF-beta cooperate in the regulatory T-cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 2003; 33:1205–1214.CrossRefPubMedGoogle Scholar
  81. 81.
    Radulovic S, Jacobson MR, Durham SR et al. Grass pollen immunotherapy induces Foxp3-expressing CD4+ CD25+ cells in the nasal mucosa. J Allergy Clin Immunol 2008; 121:1267–1272.CrossRefGoogle Scholar
  82. 82.
    Mottet C, Uhlig HH, Powrie F. Cutting edge: cure of colitis by CD4+CD25+ regulatory T-cells. J Immunol 2003; 170:3939–3943.PubMedGoogle Scholar
  83. 83.
    Pereira-Santos MC, Baptista AP, Melo A et al. Expansion of circulating Foxp3+CD25bright CD4+ T-cells during specific venom immunotherapy. Clin Exp Allergy 2008; 38:291–297.PubMedGoogle Scholar
  84. 84.
    Akdis CA, Akdis M, Blesken T et al. Epitope-specific T-cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. J Clin Invest 1996; 98:1676–1683.CrossRefPubMedGoogle Scholar
  85. 85.
    Taylor A, Verhagen J, Blaser K et al. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology 2006; 117:433–442.CrossRefPubMedGoogle Scholar
  86. 86.
    Croxford JL, Feldmann M, Chernajovsky Y et al. Different therapeutic outcomes in experimental allergic encephalomyelitis dependent upon the mode of delivery of IL-10: a comparison of the effects of protein, adenoviral or retroviral IL-10 delivery into the central nervous system. J Immunol 2001; 166:4124–4130.PubMedGoogle Scholar
  87. 87.
    Hansen G, Yeung VP, Berry G et al. Vaccination with heat-killed Listeria as adjuvant reverses established allergen-induced airway hyperreactivity and inflammation: role of CD8+ T-cells and IL-18. J Immunol 2000; 164:223–230.PubMedGoogle Scholar
  88. 88.
    Creticos PS, Schroeder JT, Hamilton RG. Immune Tolerance Network Group. Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N Engl J Med 2006; 355:1445–1455.CrossRefPubMedGoogle Scholar
  89. 89.
    Van Overtvelt L, Lombardi V, Razafindratsita A et al. IL-10-inducing adjuvants enhance sublingual immunotherapy efficacy in a murine asthma model. Int Arch Allergy Immunol 2008; 145:152–62.CrossRefPubMedGoogle Scholar

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© Landes Bioscience and Springer+Business Media 2009

Authors and Affiliations

  1. 1.Department of Allergy and Clinical ImmunologyNational Heart and Lung Institute at Imperial College LondonLondonEngland, UK

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