The role of T lymphocytes in the pathogenesis of asthma

Journal of Allergy and Clinical Immunology

Volumn 111, Issue 3, 2003, Pages 450-463

  Larché, Mark ^a   Robinson, Douglas S ^a   Kay, A Barry ^a  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

Author keywords

Airway hyperresponsiveness; Allergy; Antigen presenting cells; Asthma; Atopy; Chemokines; Immunotherapy; Remodeling; T cells; T regulatory cells; TH2 cytokines

Indexed keywords

CORTICOSTEROID; CYCLOSPORIN A; TRANSCRIPTION FACTOR GATA 3;

ALLERGY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN PRESENTING CELL; ANTIINFLAMMATORY ACTIVITY; ASTHMA; ATOPY; BRONCHUS HYPERREACTIVITY; CONTROLLED STUDY; CYTOKINE RELEASE; DRUG EFFICACY; EFFECTOR CELL; GENE TARGETING; HUMAN; HUMAN TISSUE; IMMUNE RESPONSE; IMMUNOTHERAPY; MAJOR HISTOCOMPATIBILITY COMPLEX; MOUSE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE ACTIVATION; TARGET CELL;

EID: 0037338904     PISSN: 00916749     EISSN: None     Source Type: Journal    
DOI: 10.1067/mai.2003.169     Document Type: Review

References (145)

1. Kay AB. Leukocytes in asthma. Immunol Invest 1988;17:679-705.
2. Gonzalez MC, Diaz P, Galleguillos FR, Ancic P, Cromwell O, Kay AB. Allergen-induced recruitment of bronchoalveolar helper (OKT4) and suppressor (OKT8) cells in asthma. Relative increases in OKT8 cells in single early responders compared with those in late-phase responders. Am Rev Respir Dis 1987;136:600-4.
3. Corrigan CJ, Hartnell A, Kay AB. T lymphocyte activation in acute severe asthma. Lancet 1988;1:1129-32.
4. Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 1992;326:298-304.
5. Kay AB. Allergy and allergic diseases. First of two parts. N Engl J Med 2001;344:30-7.
6. Guidelines for the diagnosis and management of asthma - update on selected topics, 2002. National Asthma Education and Prevention Program. J Allergy Clin Immunol 2002;110:S141-218.
7. Vercelli D. Immunoglobulin E and its regulators. Curr Opin Allergy Clin Immunol 2001;1:61-5.
8. Jeffery PK, Wardlaw AJ, Nelson FC, Collins JV, Kay AB. Bronchial biopsies in asthma. An ultrastructural, quantitative study and correlation with hyperreactivity. Am Rev Respir Dis 1989;140:1745-53.
9. Robinson DS, Bentley AM, Hartnell A, Kay AB, Durham SR. Activated memory T helper cells in bronchoalveolar lavage fluid from patients with atopic asthma: relation to asthma symptoms, lung function, and bronchial responsiveness. Thorax 1993;48:26-32
10. Azzawi M, Bradley B, Jeffery PK, Frew AJ, Wardlaw AJ, Knowles G, et al. Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis 1990;142:1407-13.
11. Walker C, Kaegi MK, Braun P, Blaser K. Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. J Allergy Clin Immunol 1991;88:935-42.
12. Robinson DS, Ying S, Bentley AM, Meng Q, North J, Durham SR, et al. Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytolcines, asthma symptoms, and airway methacholine responsiveness in atopic asthma. J Allergy Clin Immunol 1993;92:397-403.
13. Ying S, Humbert M, Barkans J, Corrigan CJ, Pfister R, Menz G, et al. Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics. J Immunol 1997;158:3539-44.
14. Wilson JW, Djukanovic R, Howarth PH, Holgate ST. Lymphocyte activation in bronchoalveolar lavage and peripheral blood in atopic asthma. Am Rev Respir Dis 1992;145:958-60.
15. Walker C, Bode E, Boer L, Hansel TT, Blaser K, Virchow JC Jr. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 1992;146:109-15.
16. Till S, Li B, Durham S, Humbert M, Assoufi B, Huston D, et al. Secretion of the eosinophil-active cytokines interleukin-5, granulocyte/macrophage colony-stimulating factor and interleukin-3 by bronchoalveolar lavage CD4+ and CD8+ T cell lines in atopic asthmatics, and atopic and nonatopic controls. Eur J Immunol 1995;25:2727-31.
17. Del Prete GF, De Carli M, D'Elios MM, Maestrelli P, Ricci M, Fabbri L, et al. Allergen exposure induces the activation of allergen-specific Th2 cells in the airway mucosa of patients with allergic respiratory disorders. Eur J Immunol 1993;23:1445-9.
18. Pearce N, Douwes J, Beasley R. Is allergen exposure the major primary cause of asthma? Thorax 2000;55:424-31.
19. Bentley AM, Menz G, Storz C, Robinson DS, Bradley B, Jeffery PK, et al. Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis 1992;146:500-6.
20. Bentley AM, Maestrelli P, Saetta M, Fabbri LM, Robinson DS, Bradley BL, et al. Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma. J Allergy Clin Immunol 1992;89:821-9.
21. Humbert M, Durham SR, Ying S, Kimmitt P, Barkans J, Assoufi B, et al. IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: evidence against "intrinsic" asthma being a distinct immunopathologic entity. Am J Respir Crit Care Med 1996;154:1497-504.
22. Ying S, Humbert M, Meng Q, Pfister R, Menz G, Gould HJ, et al. Local expression of epsilon germline gone transcripts and RNA for the epsilon heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma. J Allergy Clin Immunol 2001;107:686-92.
23. Valenta R, Natter S, Seiberler S, Wichlas S, Maurer D, Hess M, et al. Molecular characterization of an autoallergen, Hom s I, identified by serum IgE from atopic dermatitis patients. J Invest Dermatol 1998;111:1178-83.
24. Maestrelli P, Occari P, Turato G, Papiris SA, Di Stefano A, Mapp CE, et al. Expression of interleukin (IL)-4 and IL-5 proteins in asthma induced by toluene diisocyanate (TDI). Clin Exp Allergy 1997;27:1292-8.
25. Azzawi M, Johnston PW, Majumdar S, Kay AB, Jeffery PK. T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis. Am Rev Respir Dis 1992;145:1477-82
26. Busse WW, Banks-Schlegel S, Wenzel SE. Pathophysiology of severe asthma. J Allergy Clin Immunol 2000;106:1033-42.
27. Hamid Q, Song Y, Kotsimbos TC, Minshall E, Bai TR, Hegele RG, et al. Inflammation of small airways in asthma. J Allergy Clin Immunol 1997;100:44-51.
28. Krug N, Madden J, Redington AE, Lackie P, Djukanovic R, Schauer U, et al. T-cell cytokine profile evaluated at the single cell level in BAL and blood in allergic asthma. Am J Respir Cell Mol Biol 1996;14:319-26.
29. Lacy P, Moqbel R. Immune effector functions of eosinophils in allergic airway inflammation. Curr Opin Allergy Clin Immunol 2001;1:79-84.
30. Pawankar R. Mast cells as orchestrators of the allergic reaction: the IgE-IgE receptor mast cell network. Curr Opin Allergy Clin Immunol 2001;1:3-6.
31. Bradding P, Roberts JA, Britten KM, Montefort S, Djukanovic R, Mueller R, et al. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol 1994;10:471-80.
32. Hakonarson H, Maskeri N, Carter C, Chuang S, Grunstein MM. Autocrine interaction between IL-5 and IL-1beta mediates altered responsiveness of atopic asthmatic sensitized airway smooth muscle. J Clin Invest 1999;104:657-67.
33. Laporte JC, Moore PE, Baraldo S, Jouvin MH, Church TL, Schwartzman IN, et al. Direct effects of interleukin-13 on signaling pathways for physiological responses in cultured human airway smooth muscle cells. Am J Respir Crit Care Med 2001;164:141-8.
34. Chiappara G, Gagliardo R, Siena A, Bonsignore MR, Bousquet J, Bonsignore G, et al. Airway remodelling in the pathogenesis of asthma. Curr Opin Allergy Clin Immunol 2001;1:85-93.
35. Maclem PT. A theoretical analysis of the effect of airway smooth muscle load on airway narrowing. Am J Respir Crit Care Med 1996;153:83-9.
36. Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID. Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med 2002;346:1699-705.
37. Lloyd CM, Gonzalo JA, Coyle AJ, Gutierrez-Ramos JC. Mouse models of allergic airway disease. Adv Immunol 2001;77:263-95.
38. Corry DB, Folkesson HG, Warnock ML, Erle DJ, Matthay MA, Wiener-Kronish JP, et al. Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J Exp Med 1996;183:109-17.
39. Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med 1996;183:195-201.
40. Nicolaides NC, Holroyd KJ, Ewart SL, Eleff SM, Kiser MB, Dragwa CR, et al. Interleukin 9: a candidate gene for asthma. Proc Natl Acad Sci U S A 1997;94:13175-80.
41. Temann UA, Geba GP, Rankin JA, Flavell RA. Expression of interleukin 9 in the lungs of transgenic mice causes airway inflammation, mast cell hyperplasia, and bronchial hyperresponsiveness. J Exp Med 1998;188:1307-20.
42. McMillan SJ, Bishop B, Townsend MJ, McKenzie AN, Lloyd CM. The absence of interleukin 9 does not affect the development of allergen-induced pulmonary inflammation nor airway hyperreactivity. J Exp Med 2002;195:51-7.
43. Tang W, Geba GP, Zheng T, Ray P, Homer RJ, Kuhn C 3rd, et al. Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction. J Clin Invest 1996;98:2845-53.
44. Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999;103:779-88.
45. Wang J, Homer RJ, Hong L, Cohn L, Lee CG, Jung S, et al. IL-11 selectively inhibits aeroallergen-induced pulmonary eosinophilia and Th2 cytokine production. J Immunol 2000;165:2222-31.
46. Curti A, Ratta M, Corinti S, Girolomoni G, Ricci F, Tazzari P, et al. Interleukin-11 induces Th2 polarization of human CD4(+) T cells. Blood 2001;97:2758-63.
47. Grunig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, Rennick DM, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 1998;282:2261-3.
48. Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, et al. Interleukin-13: central mediator of allergic asthma. Science 1998;282:2258-61.
49. Hogan SP, Matthaei KI, Young JM, Koskinen A, Young IG, Foster PS. A novel T cell-regulated mechanism modulating allergen-induced airways hyperreactivity in BALB/c mice independently of IL-4 and IL-5. J Immunol 1998;161:1501-9.
50. Mattes J, Yang M, Mahalingam S, Kuehr J, Webb DC, Simson L, et al. Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreactivity in experimental asthma. J Exp Med 2002;195:1433-44.
51. Center DM, Kornfeld H, Wu MJ, Falvo M, Theodore AC, Bernardo J, et al. Cytokine binding to CD4+ inflammatory cells: implications for asthma. Am J Respir Crit Care Med 1994;150:S59-62.
52. Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Page N, et al. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 2001;108:430-8.
53. Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S, et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 2001;15:985-95.
54. Hurst SD, Muchamuel T, Gorman DM, Gilbert JM, Clifford T, Kwan S, et al. New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo function of the novel cytokine IL-25. J Immunol 2002;169:443-53.
55. Ying S, Meng Q, Kay AB, Robinson DS. Elevated expression of interleukin-9 mRNA in the bronchial mucosa of atopic asthmatics and allergen-induced cutaneous late-phase reaction: relationships to eosinophils, mast cells and T lymphocytes. Clin Exp Allergy 2002;32:866-71.
56. Minshall E, Chakir J, Laviolette M, Molet S, Zhu Z, Olivenstein R, et al. IL-11 expression is increased in severe asthma: association with epithelial cells and eosinophils. J Allergy Clin Immunol 2000;105:232-8.
57. Humbert M, Durham SR, Kimmitt P, Powell N, Assoufi B, Pfister R, et al. Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma. J Allergy Clin Immunol 1997;99:657-65.
58. Laberge S, Ernst P, Ghaffar O, Cruikshank WW, Kornfeld H, Center DM, et al. Increased expression of interleukin-16 in bronchial mucosa of subjects with atopic asthma. Am J Respir Cell Mol Biol 1997;17:193-202.
59. Gavett SH, O'Hearn DJ, Li X, Huang SK, Finkelman FD, Wills-Karp M. Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice. J Exp Med 1995;182:1527-36.
60. Kodama T, Matsuyama T, Kuribayashi K, Nishioka Y, Sugita M, Akira S, et al. IL-18 deficiency selectively enhances allergen-induced eosinophilia in mice. J Allergy Clin Immunol 2000;105:45-53.
61. Hofstra CL, Van Ark I, Hofman G, Kool M, Nijkamp FP, Van Oosterhout AJ. Prevention of Th2-like cell responses by coadministration of IL-12 and IL-18 is associated with inhibition of antigen-induced airway hyperresponsiveness, eosinophilia, and serum IgE levels. J Immunol 1998;161:5054-60.
62. Ho LP, Davis M, Denison A, Wood FT, Greening AP. Reduced interleukin-18 levels in BAL specimens from patients with asthma compared to patients with sarcoidosis and healthy control subjects. Chest 2002;121:1421-6.
63. Naseer T, Minshall EM, Leung DY, Laberge S, Ernst P, Martin RJ, et al. Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy. Am J Respir Crit Care Med 1997;155:845-51.
64. Robinson DS, Lloyd CM. Asthma: T-bet - a master controller? Curr Biol 2002;12:R322-4.
65. Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 1997;89:587-96.
66. Zhang DH, Yang L, Cohn L, Parkyn L, Homer R, Ray P, et al. Inhibition of allergic inflammation in a routine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 1999;11:473-82.
67. Finotto S, De Sanctis GT, Lehr HA, Herz U, Buerke M, Schipp M, et al. Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression. J Exp Med 2001;193:1247-60.
68. Das J, Chen CH, Yang L, Cohn L, Ray P, Ray A. A critical role for NF-kappa B in GATA3 expression and TH2 differentiation in allergic airway inflammation. Nat Immunol 2001;2:45-50.
69. Nakamura Y, Ghaffar O, Olivenstein R, Taha RA, Soussi-Gounni A, Zhang DH, et al. Gene expression of the GATA-3 transcription factor is increased in atopic asthma. J Allergy Clin Immunol 1999;103:215-22.
70. Christodoulopoulos P, Cameron L, Nakamura Y, Lemiere C, Muro S, Dugas M, et al. TH2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression. J Allergy Clin Immunol 2001;107:586-91.
71. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 2000;100:655-69.
72. Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, et al. T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat Immunol 2002;3:549-57.
73. Finotto S, Neurath MF, Glickman JN, Qin S, Lehr HA, Green FH, et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 2002;295:336-8.
74. Cousins DJ, Lee TH, Staynov DZ. Cytokine coexpression during human Th1/Th2 cell differentiation: direct evidence for coordinated expression of Th2 cytokines. J Immunol 2002;169:2498-506.
75. O'Byrne PM, Dolovich J, Hargreave FE. Late asthmatic responses. Am Rev Respir Dis 1987;136:740-51.
76. Solley GO, Gleich GJ, Jordon RE, Schroeter AL. The late phase of the immediate wheal and flare skin reaction. Its dependence upon IgE antibodies. J Clin Invest 1976;58:408-20.
77. Frew AJ, Kay AB. The relationship between infiltrating CD4+ lymphocytes, activated eosinophils, and the magnitude of the allergen-induced late phase cutaneous reaction in man. J Immunol 1988;141:4158-64.
78. Kay AB, Ying S, Varney V, Gaga M, Durham SR, Moqbel R, et al. Messenger RNA expression of the cytokine gone cluster, interleukin 3 (IL-3), IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor, in allergen-induced late-phase cutaneous reactions in atopic subjects. J Exp Med 1991;173:775-8.
79. + T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J Allergy Clin Immunol 1993;92:313-24.
80. Bentley AM, Meng Q, Robinson DS, Hamid Q, Kay AB, Durham SR. Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for interleukin-5 and granulocyte/macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation challenge in atopic asthmatics. Am J Respir Cell Mol Biol 1993;8:35-42.
81. Sihra BS, Kon OM, Durham SR, Walker S, Barnes NC, Kay AB. Effect of cyclosporin A on the allergen-induced late asthmatic reaction. Thorax 1997;52:447-52.
82. Casolaro V, Spadaro G, Patella V, Marone G. In vivo characterization of the anti-inflammatory effects of cyclosporin A on human basophils. J Immunol 1993;151:5563-73.
83. 2 release from human lung mast cells by ciclosporin A. Int Arch Allergy Appl Immunol 1989;88:253-5.
84. Khan LN, Kon OM, Macfarlane AJ, Meng Q, Ying S, Barnes NC, et al. Attenuation of the allergen-induced late asthmatic reaction by cyclosporin A is associated with inhibition of bronchial eosinophils, interleukin-5, granulocyte macrophage colony-stimulating factor, and eotaxin. Am J Respir Crit Care Med 2000;162:1377-82.
85. Haselden BM, Kay AB, Larché M. Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitope-induced late asthmatic reactions. J Exp Med 1999;189:1885-94.
86. Haselden BM, Larche M, Meng Q, Shirley K, Dworski R, Kaplan AP, et al. Late asthmatic reactions provoked by intradermal injection of T-cell peptide epitopes are not associated with bronchial mucosa infiltration of eosinophils or TH2-type cells or with elevated concentrations of histamine or eicosanoids in bronchoalveolar fluid. J Allergy Clin Immunol 2001;108:394-401.
87. Ali FR, Bylanski M, Arbery J, Larché M, Kay AB. Inhalation of allergen-derived T cell epitopes induces isolated late asthmatic reactions with associated local eosinophilia. J Allergy Clin Immunol 2002;109:S167.
88. Tseng SY, Dustin ML. T cell activation: a multidimensional signalling network. Curr Opin Cell Biol 2002;14:575-80.
89. Shortman K, Liu YJ. Mouse and human dendritic cell subtypes. Nat Rev Immunol 2002;2:151-61.
90. Akbari O, Freeman GJ, Meyer EH, Greenfield EA, Chang TT, Sharpe AH, et al. Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med 2002;8:1024-32.
91. Gonzalo JA, Tian J, Delaney T, Corcoran J, Rottman JB, Lora J, et al. ICOS is critical for T helper cell-mediated lung mucosa inflammatory responses. Nat Immunol 2001;2:597-604.
92. Larche M, Till SJ, Haselden BM, North J, Barkans J, Corrigan CJ, et al. Costimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics. J Immunol 1998;161:6375-82.
93. Caron G, Delneste Y, Roelandts E, Duez C, Bonnefoy JY, Pestel J, et al. Histamine polarizes human dendritic cells into Th2 cell-promoting effector dendritic cells. J Immunol 2001;167:3682-6.
94. Cho SH, Stanciu LA, Begishivili T, Bates PJ, Holgate ST, Johnston SL. Peripheral blood CD4+ and CD8+ T cell type 1 and type 2 cytokine production in atopic asthmatic and normal subjects. Clin Exp Allergy 2002;32:427-33.
95. Maestrelli P, Del Prete GF, De Carli M, D'Elios MM, Saetta M, Di Stefano A, et al. CD8 T-cell clones producing interleukin-5 and interferon-gamma in bronchial mucosa of patients with asthma induced by toluene diisocyanate. Scand J Work Environ Health 1994;20:376-81.
96. Schwarze J, Cieslewicz G, Joetham A, Ikemura T, Hamelmann E, Gelfand EW. CD8 T cells are essential in the development of respiratory syncytial virus-induced lung eosinophilia and airway hyperresponsiveness. J Immunol 1999;162:4207-11.
97. McMenamin C, Pimm C, McKersey M, Holt PG. Regulation of IgE responses to inhaled antigen in mice by antigen-specific gamma delta T cells. Science 1994;265:1869-71.
98. Lahn M, Kanehiro A, Takeda K, Joetham A, Schwarze J, Kohler G, et al. Negative regulation of airway responsiveness that is dependent on gammadelta T cells and independent of alphabeta T cells. Nat Med 1999;5:1150-6.
99. Zuany-Amorim C, Ruffie C, Haile S, Vargaftig BB, Pereira P, Pretolani M. Requirement for gammadelta T cells in allergic airway inflammation. Science 1998;280:1265-7.
100. Krug N, Erpenbeck VJ, Balke K, Petschallies J, Tschernig T, Hohlfeld JM, et al. Cytokine profile of bronchoalveolar lavage-derived CD4(+), CD8(+), and gammadelta T cells in people with asthma after segmental allergen challenge. Am J Respir Cell Mol Biol 2001;25:125-31.
101. Spinozzi F, Agea E, Bistoni O, Forenza N, Monaco A, Bassotti G, et al. Increased allergen-specific, steroid-sensitive gamma delta T cells in bronchoalveolar lavage fluid from patients with asthma. Ann Intern Med 1996;124:223-7.
102. Chen KS, Miller KH, Hengehold D. Diminution of T cells with gamma delta receptor in the peripheral blood of allergic asthmatic individuals. Clin Exp Allergy 1996;26:295-302.
103. Lloyd CM, Delaney T, Nguyen T, Tian J, Martinez AC, Coyle AJ, et al. CC chemokine receptor (CCR)3/eotaxin is followed by CCR4/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo. J Exp Med 2000;191:265-74.
104. Humbles AA, Lu B, Friend DS, Okinaga S, Lora J, Al-Garawi A, et al. The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc Natl Acad Sci U S A 2002;99:1479-84.
105. Chvatchko Y, Hoogewerf AJ, Meyer A, Alouani S, Juillard P, Buser R, et al. A key role for CC chemokine receptor 4 in lipopolysaccharide-induced endotoxic shock. J Exp Med 2000;191:1755-64.
106. Schuh JM, Power CA, Proudfoot AE, Kunkel SL, Lukacs NW, Hogaboam CM. Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4-/- mice. FASEB J 2002;16:1313-5.
107. Chensue SW, Lukacs NW, Yang TY, Shang X, Frait KA, Kunkel SL, et al. Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice. J Exp Med 2001;193:573-84.
108. Oliveira SH, Lira S, Martinez AC, Wiekowski M, Sullivan L, Lukacs NW. Increased responsiveness of murine eosinophils to MIP-1β (CCL4) and TCA-3 (CCL1) is mediated by their specific receptors, CCR5 and CCR8. J Leukoc Biol 2002;71:1019-25.
109. Panina-Bordignon P, Papi A, Mariani M, Di Lucia P, Casoni G, Bellettato C, et al. The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. J Clin Invest 2001;107:1357-64.
110. Campbell JJ, Brightling CE, Symon FA, Qin S, Murphy KE, Hodge M, et al. Expression of chemokine receptors by lung T cells from normal and asthmatic subjects. J Immunol 2001;166:2842-8.
111. Barnes PJ. Current issues for establishing inhaled corticosteroids as the antiinflammatory agents of choice in asthma. J Allergy Clin Immunol 1998;101:S427-33.
112. Robinson D, Hamid Q, Ying S, Bentley A, Assoufi B, Durham S, et al. Prednisolone treatment in asthma is associated with modulation of bronchoalveolar lavage cell interleukin-4, interleukin-5, and interferon-gamma cytokine gene expression. Am Rev Respir Dis 1993;148:401-6.
113. Bentley AM, Hamid Q, Robinson DS, Schotman E, Meng Q, Assoufi B, et al. Prednisolone treatment in asthma. Reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa. Am J Respir Crit Care Med 1996;153:551-6.
114. Leung DY, Martin RJ, Szefler SJ, Sher ER, Ying S, Kay AB, et al. Dysregulation of interleukin 4, interleukin 5, and interferon gamma gene expression in steroid-resistant asthma. J Exp Med 1995;181:33-40.
115. Kam JC, Szefler SJ, Surs W, Sher ER, Leung DY. Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids. J Immunol 1993;151:3460-6.
116. Goleva E, Kisich KO, Leung DY. A Role for STAT5 in the pathogenesis of IL-2-induced glucocorticoid resistance. J Immunol 2002;169:5934-40.
117. Adcock IM, Lane SJ, Brown CR, Lee TH, Barnes PJ. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med 1995;182:1951-8.
118. Alexander AG, Barnes NC, Kay AB, Corrigan CJ. Can clinical response to cyclosporin in chronic severe asthma be predicted by an in vitro T-lymphocyte proliferation assay? Eur Respir J 1996;9:1421-6.
119. Lock SH, Kay AB, Barnes NC. Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma. Am J Respir Crit Care Med 1996:153:509-14.
120. Nizankowska E, Soja J, Pinis G, Bochenek G, Sladek K, Domagala B, et al. Treatment of steroid-dependent bronchial asthma with cyclosporin. Eur Respir J 1995;8:1091-9.
121. Kon OM, Sihra BS, Compton CH, Leonard TB, Kay AB, Barnes NC. Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma. Lancet 1998;352:1109-13.
122. Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. Anti-IL-5 (mepolizumab) only partially depletes eosinophils from asthmatic airway tissue. Am J Respir Crit Care Med 2003;167:199-204.
123. Leckie MJ, ten Brinke A, Khan J, Diamant Z, O'Connor BJ, Walls CM, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000;356:2144-8.
124. Borish LC, Nelson HS, Corren J, Bensch G, Busse WW, Whitmore JB, et al. IL-4R Asthma Study Group. Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol 2001;107:963-70.
125. Borish LC, Nelson HS, Lanz MJ, Claussen L, Whitmore JB, Agosti JM, et al. Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med 199;160:1816-23.
126. Durham SR, Till SJ. Immunologic changes associated with allergen immunotherapy. J Allergy Clin Immunol 1998;102:157-64.
127. Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY. IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol 1998;160:3555-61.
128. Barnes PJ. Is immunotherapy for asthma worthwhile? N Engl J Med 1996;334:531-2.
129. Briner TJ, Kuo MC, Keating KM, Rogers BL, Greenstein JL. Peripheral T-cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen Fel d 1. Proc Natl Acad Sci U S A 1993;90:7608-12.
130. Norman PS, Ohman JL Jr, Long AA, Creticos PS, Gefter MA, Shaked Z, et al. Treatment of cat allergy with T-cell reactive peptides. Am J Respir Crit Care Med 1996;154:1623-8.
131. Simons FE, Imada M, Li Y, Watson WT, HayGlass KT. Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects. Int Immunol 1996;8:1937-45.
132. Pene J, Desroches A, Paradis L, Lebel B, Farce M, Nicodemus CF, et al. Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats. J Allergy Clin Immunol 1998;102:571-8.
133. Maguire P, Nicodemus C, Robinson D, Aaronson D, Umetsu DT. The safety and efficacy of ALLERVAX CAT in cat allergic patients. Clin Immunol 1999;93:222-31.
134. Webb S, Morris C, Sprent J. Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell 1990;63:1249-56.
135. Vidard L, Colarusso LJ, Benacerraf B. Specific T-cell tolerance may be preceded by a primary response. Proc Natl Acad Sci U S A 1994;91:5627-31.
136. Hoyne GF, Askonas BA, Hetzel C, Thomas WR, Lamb JR. Regulation of house dust mite responses by intranasally administered peptide: transient activation of CD4+ T cells precedes the development of tolerance in vivo. Int Immunol 1996;8:335-42.
137. Tsitoura DC, DeKruyff RH, Lamb JR, Umetsu DT. Intranasal exposure to protein antigen induces immunological tolerance mediated by functionally disabled CD4+ T cells. J Immunol 1999;163:2592-600.
138. Oldfield WLG, Kay AB, Larche M. Allergen-derived T cell peptide-induced late asthmatic reactions precede the induction of antigen-specific hyporesponsiveness in atopic allergic asthmatic subjects. J Immunol 2001;167:1734-9.
139. Oldfield WLG, Larche M, Kay AB. Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial. Lancet 2002;360:47-53.
140. Müller U, Akdis CA, Fricker M, Akdis M, Blesken T, Bettens F, et al. Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. J Allergy Clin Immunol 1998;101:747-54.
141. Moller C, Dreborg S, Ferdousi HA, Halken S, Host A, Jacobsen L, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 2002;109:251-6.
142. McHugh RS, Shevach EM. The role of suppressor T cells in regulation of immune responses. J Allergy Clin Immunol 2002;110:693-702.
143. Barrat FJ, Cua DJ, Boonstra A, Richards DF, Crain C, Savelkoul HF, et al. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med 2002;195:603-16.
144. Richards DF, Fernandez M, Caulfield J, Hawrylowicz CM. Glucocorticoids drive human CD8(+) T cell differentiation towards a phenotype with high IL-10 and reduced IL-4, IL-5 and IL-13 production. Eur J Immunol 2000;30:2344-54.
145. Hawrylowicz C, Richards D, Loke TK, Corrigan C, Lee T. A defect in corticosteroid-induced IL-10 production in T lymphocytes from corticosteroid-resistant asthmatic patients. J Allergy Clin Immunol 2002;109:369-70.