To respond or not to respond: T cells in allergic asthma (original) (raw)

• Holgate, S. T. The epidemic of allergy and asthma. Nature 402, B2–B4 (1999).
  CAS PubMed Google Scholar
• Umetsu, D. T., McIntire, J. J., Akbari, O., Macaubas, C. & DeKruyff, R. H. Asthma: an epidemic of dysregulated immunity. Nature Immunol. 3, 715–720 (2002).
  CAS Google Scholar
• Cookson, W. The alliance of genes and environment in asthma and allergy. Nature 402, B5–B11 (1999).
  CAS PubMed Google Scholar
• Strachan, D. P. Hay fever, hygiene, and household size. BMJ 299, 1259–1260 (1989).
  CAS PubMed PubMed Central Google Scholar
• Strachan, D. P. Family size, infection and atopy: the first decade of the 'hygiene hypothesis'. Thorax 55 Suppl. 1, S2–S10 (2000).
  PubMed PubMed Central Google Scholar
• von Mutius, E. et al. Skin test reactivity and number of siblings. BMJ 308, 692–695 (1994).
  CAS PubMed PubMed Central Google Scholar
• Kramer, U., Heinrich, J., Wjst, M. & Wichmann, H. E. Age of entry to day nursery and allergy in later childhood. Lancet 353, 450–454 (1999).
  CAS PubMed Google Scholar
• Ball, T. M. et al. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N. Engl. J. Med. 343, 538–543 (2000).
  CAS PubMed Google Scholar
• Busse, W. W. & Lemanske, R. F. Jr. Asthma. N. Engl. J. Med. 344, 350–362 (2001).
  CAS PubMed Google Scholar
• Kim, J., Woods, A., Becker-Dunn, E. & Bottomly, K. Distinct functional phenotypes of cloned Ia-restricted helper T cells. J. Exp. Med. 162, 188–201 (1985).
  CAS PubMed Google Scholar
• Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. & Coffman, R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348–2357 (1986).
  CAS PubMed Google Scholar
• van Reijsen, F. C. et al. Skin-derived aeroallergen-specific T-cell clones of TH2 phenotype in patients with atopic dermatitis. J. Allergy Clin. Immunol. 90, 184–192 (1992).
  CAS PubMed Google Scholar
• Robinson, D. S. et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N. Engl. J. Med. 326, 298–304 (1992).
  CAS PubMed Google Scholar
• Walker, C. et al. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am. Rev. Respir. Dis. 146, 109–115 (1992).
  CAS PubMed Google Scholar
• Robinson, D. et al. Activation of CD4+ 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. 92, 313–324 (1993).
  CAS PubMed Google Scholar
• Hamid, Q., Boguniewicz, M. & Leung, D. Y. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J. Clin. Invest. 94, 870–876 (1994).
  CAS PubMed PubMed Central Google Scholar
• Huang, S. K. et al. IL-13 expression at the sites of allergen challenge in patients with asthma. J. Immunol. 155, 2688–2694 (1995).
  CAS PubMed Google Scholar
• Hamid, Q. et al. In vivo expression of IL-12 and IL-13 in atopic dermatitis. J. Allergy Clin. Immunol. 98, 225–231 (1996).
  CAS PubMed Google Scholar
• Nakajima, H. et al. CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. Am. Rev. Respir. Dis. 146, 374–377 (1992).
  CAS PubMed Google Scholar
• Gavett, S. H., Chen, X., Finkelman, F. & Wills-Karp, M. Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia. Am. J. Respir. Cell. Mol. Biol. 10, 587–593 (1994).
  CAS PubMed Google Scholar
• Brusselle, G. G. et al. Attenuation of allergic airway inflammation in IL-4 deficient mice. Clin. Exp. Allergy 24, 73–80 (1994).
  CAS PubMed Google Scholar
• Cohn, L., Tepper, J. S. & Bottomly, K. IL-4-independent induction of airway hyperresponsiveness by TH2, but not TH1, cells. J. Immunol. 161, 3813–3816 (1998).
  CAS PubMed Google Scholar
• Coyle, A. J. et al. Interleukin-4 is required for the induction of lung TH2 mucosal immunity. Am. J. Respir. Cell. Mol. Biol. 13, 54–59 (1995).
  CAS PubMed Google Scholar
• Kips, J. C. et al. Importance of interleukin-4 and interleukin-12 in allergen-induced airway changes in mice. Int. Arch. Allergy Immunol. 107, 115–118 (1995).
  CAS PubMed Google Scholar
• Corry, D. B. et al. Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J. Exp. Med. 183, 109–117 (1996).
  CAS PubMed Google Scholar
• Herrick, C. A., MacLeod, H., Glusac, E., Tigelaar, R. E. & Bottomly, K. TH2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4. J. Clin. Invest. 105, 765–775 (2000).
  CAS PubMed PubMed Central Google Scholar
• Schwarze, J. et al. CD8 T cells are essential in the development of respiratory syncytial virus-induced lung eosinophilia and airway hyperresponsiveness. J. Immunol. 162, 4207–4211 (1999).
  CAS PubMed Google Scholar
• Schwarze, J. et al. Transfer of the enhancing effect of respiratory syncytial virus infection on subsequent allergic airway sensitization by T lymphocytes. J. Immunol. 163, 5729–5734 (1999).
  CAS PubMed Google Scholar
• Abbas, A. K., Murphy, K. M. & Sher, A. Functional diversity of helper T lymphocytes. Nature 383, 787–793 (1996).
  CAS PubMed Google Scholar
• Shirakawa, T., Enomoto, T., Shimazu, S. & Hopkin, J. M. The inverse association between tuberculin responses and atopic disorder. Science 275, 77–79 (1997).
  CAS PubMed Google Scholar
• Shaheen, S. O. et al. Measles and atopy in Guinea-Bissau. Lancet 347, 1792–1796 (1996).
  CAS PubMed Google Scholar
• von Hertzen, L., Klaukka, T., Mattila, H. & Haahtela, T. Mycobacterium tuberculosis infection and the subsequent development of asthma and allergic conditions. J. Allergy Clin. Immunol. 104, 1211–1214 (1999).
  CAS PubMed Google Scholar
• Fonager, K., Sorensen, H. T. & Olsen, J. Change in incidence of Crohn's disease and ulcerative colitis in Denmark. A study based on the National Registry of Patients, 1981–1992. Int. J. Epidemiol. 26, 1003–1008 (1997).
  CAS PubMed Google Scholar
• Armitage, E., Drummond, H. E., Wilson, D. C. & Ghosh, S. Increasing incidence of both juvenile-onset Crohn's disease and ulcerative colitis in Scotland. Eur. J. Gastroenterol. Hepatol. 13, 1439–1447 (2001).
  CAS PubMed Google Scholar
• Onkamo, P., Vaananen, S., Karvonen, M. & Tuomilehto, J. Worldwide increase in incidence of type I diabetes — the analysis of the data on published incidence trends. Diabetologia 42, 1395–1403 (1999).
  CAS PubMed Google Scholar
• van den Biggelaar, A. H. et al. The prevalence of parasite infestation and house dust mite sensitization in Gabonese schoolchildren. Int. Arch. Allergy Immunol. 126, 231–238 (2001).
  CAS PubMed Google Scholar
• Yazdanbakhsh, M., van den Biggelaar, A. & Maizels, R. M. TH2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease. Trends Immunol. 22, 372–377 (2001).
  CAS PubMed Google Scholar
• Cohn, L. et al. TH2-induced airway mucus production is dependent on IL-4Rα, but not on eosinophils. J. Immunol. 162, 6178–6183 (1999).
  CAS PubMed Google Scholar
• Hansen, G., Berry, G., DeKruyff, R. H. & Umetsu, D. T. Allergen-specific TH1 cells fail to counterbalance TH2 cell-induced airway hyperreactivity but cause severe airway inflammation. J. Clin. Invest. 103, 175–183 (1999).
  CAS PubMed PubMed Central Google Scholar
• Huang, T. J. et al. Allergen-specific TH1 cells counteract efferent TH2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-γ. J. Immunol. 166, 207–217 (2001).
  CAS PubMed Google Scholar
• Hogan, S. P., Mould, A., Kikutani, H., Ramsay, A. J. & Foster, P. S. Aeroallergen-induced eosinophilic inflammation, lung damage, and airways hyperreactivity in mice can occur independently of IL-4 and allergen-specific immunoglobulins. J. Clin. Invest. 99, 1329–1339 (1997).
  CAS PubMed PubMed Central Google Scholar
• Cohn, L., Herrick, C., Niu, N., Homer, R. & Bottomly, K. IL-4 promotes airway eosinophilia by suppressing IFN-γ production: defining a novel role for IFN-γ in the regulation of allergic airway inflammation. J. Immunol. 166, 2760–2767 (2001).
  CAS PubMed Google Scholar
• Li, L., Xia, Y., Nguyen, A., Feng, L. & Lo, D. TH2-induced eotaxin expression and eosinophilia coexist with TH1 responses at the effector stage of lung inflammation. J. Immunol. 161, 3128–3135 (1998).
  CAS PubMed Google Scholar
• Randolph, D. A., Stephens, R., Carruthers, C. J. & Chaplin, D. D. Cooperation between TH1 and TH2 cells in a murine model of eosinophilic airway inflammation. J. Clin. Invest. 104, 1021–1029 (1999).
  CAS PubMed PubMed Central Google Scholar
• Boguniewicz, M. et al. The effects of nebulized recombinant interferon-γ in asthmatic airways. J. Allergy Clin. Immunol. 95, 133–135 (1995).
  CAS PubMed Google Scholar
• Martin, R. J. et al. The effects of inhaled interferon-γ in normal human airways. Am. Rev. Respir. Dis. 148, 1677–1682 (1993).
  CAS PubMed Google Scholar
• Tournoy, K. G., Kips, J. C. & Pauwels, R. A. Is TH1 the solution for TH2 in asthma? Clin. Exp. Allergy 32, 17–29 (2002).
  CAS PubMed Google Scholar
• Wills-Karp, M., Santeliz, J. & Karp, C. L. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nature Rev. Immunol. 1, 69–75. (2001).
  CAS Google Scholar
• Yssel, H., Lecart, S. & Pene, J. Regulatory T cells and allergic asthma. Microbes Infect. 3, 899–904 (2001).
  CAS PubMed Google Scholar
• Shevach, E. M. CD4+ CD25+ suppressor T cells: more questions than answers. Nature Rev. Immunol. 2, 389–400 (2002).
  CAS Google Scholar
• Read, S. & Powrie, F. CD4+ regulatory T cells. Curr. Opin. Immunol. 13, 644–649 (2001).
  CAS PubMed Google Scholar
• McGuirk, P., McCann, C. & Mills, K. H. Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J. Exp. Med. 195, 221–231 (2002). This study provides evidence that microbial antigens can induce regulatory T cells and is the first demonstration of pathogen-specific T regulatory type 1 (T R 1) cells.
  CAS PubMed PubMed Central Google Scholar
• McGuirk, P. & Mills, K. H. Pathogen-specific regulatory T cells provoke a shift in the TH1/TH2 paradigm in immunity to infectious diseases. Trends Immunol. 23, 450–455 (2002).
  CAS PubMed Google Scholar
• Seymour, B. W., Gershwin, L. J. & Coffman, R. L. Aerosol-induced immunoglobulin (Ig)-E unresponsiveness to ovalbumin does not require CD8+ or T cell receptor (TCR)-γδ+ T cells or interferon (IFN)-γ in a murine model of allergen sensitization. J. Exp. Med. 187, 721–731 (1998).
  CAS PubMed PubMed Central Google Scholar
• Tsitoura, D. C., DeKruyff, R. H., Lamb, J. R. & Umetsu, D. T. Intranasal exposure to protein antigen induces immunological tolerance mediated by functionally disabled CD4+ T cells. J. Immunol. 163, 2592–2600 (1999).
  CAS PubMed Google Scholar
• Akbari, O., DeKruyff, R. H. & Umetsu, D. T. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nature Immunol. 2, 725–731 (2001).
  CAS Google Scholar
• Schwartz, R. H. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71, 1065–1068 (1992).
  CAS PubMed Google Scholar
• Medzhitov, R. Toll-like receptors and innate immunity. Nature Rev. Immunol. 1, 135–145 (2001).
  CAS Google Scholar
• Janeway, C. A. Jr & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197–216 (2002).
  CAS PubMed Google Scholar
• Zuany-Amorim, C. et al. Suppression of airway eosinophilia by killed _Mycobacterium vaccae_- induced allergen-specific regulatory T-cells. Nature Med. 8, 625–629 (2002). This paper shows that prior exposure to microbial antigens can suppress the subsequent generation of an antigen-specific airway inflammatory response.
  CAS PubMed Google Scholar
• Wakkach, A. et al. Characterization of dendritic cells that induce tolerance and T regulatory 1 cells differentiation in vivo. Immunity (in the press).
• Holt, P. G., Batty, J. E. & Turner, K. J. Inhibition of specific IgE responses in mice by pre-exposure to inhaled antigen. Immunology 42, 409–417 (1981).
  CAS PubMed PubMed Central Google Scholar
• Akbari, O. et al. Antigen-specific regulatory T cells develop via the ICOS–ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nature Med. 8, 1024–1032 (2002). This study shows both the ability of inhaled antigen to induce a population of dendritic cells (DCs), which can then induce regulatory T cells in vitro , as well as the capacity of regulatory T cells to suppress airway inflammatory responses.
  CAS PubMed Google Scholar
• Eisenbarth, S. C. et al. Lipopolysaccharide-enhanced, Toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J. Exp. Med. 196, 1645–1651 (2002). This study shows that the generation of T H 2-cell responses in the airways is dependent on the innate immune system signalling through Toll-like receptor 4 (TLR4) and provides a probable mechanism involving DC maturation.
  CAS PubMed PubMed Central Google Scholar
• Dabbagh, K., Dahl, M. E., Stepick-Biek, P. & Lewis, D. B. Toll-like receptor 4 is required for optimal development of TH2 immune responses: role of dendritic cells. J. Immunol. 168, 4524–4530 (2002).
  CAS PubMed Google Scholar
• von Mutius, E. et al. Exposure to endotoxin or other bacterial components might protect against the development of atopy. Clin. Exp. Allergy 30, 1230–1234 (2000).
  CAS PubMed Google Scholar
• Park, J. H., Gold, D. R., Spiegelman, D. L., Burge, H. A. & Milton, D. K. House dust endotoxin and wheeze in the first year of life. Am. J. Respir. Crit. Care Med. 163, 322–328 (2001).
  CAS PubMed Google Scholar
• Reed, C. E. & Milton, D. K. Endotoxin-stimulated innate immunity: a contributing factor for asthma. J. Allergy Clin. Immunol. 108, 157–166 (2001).
  CAS PubMed Google Scholar
• Jonuleit, H., Schmitt, E., Schuler, G., Knop, J. & Enk, A. H. Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J. Exp. Med. 192, 1213–1222 (2000).
  CAS PubMed PubMed Central Google Scholar
• Barnes, P. F. et al. Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. J. Immunol. 149, 541–547 (1992).
  CAS PubMed Google Scholar
• Van der Kleij, D. et al. Triggering of innate immune responses by schistosome egg glycolipids and their carbohydrate epitope GalNAc β1–4(Fuc α1–2Fuc α1–3)GlcNAc. J. Infect. Dis. 185, 531–539 (2002).
  CAS PubMed Google Scholar
• Mahanty, S. et al. High levels of spontaneous and parasite antigen-driven interleukin-10 production are associated with antigen-specific hyporesponsiveness in human lymphatic filariasis. J. Infect. Dis. 173, 769–773 (1996).
  CAS PubMed Google Scholar
• Gale, E. A. A missing link in the hygiene hypothesis? Diabetologia 45, 588–594 (2002).
  CAS PubMed Google Scholar
• Chen, Y., Kuchroo, V. K., Inobe, J., Hafler, D. A. & Weiner, H. L. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265, 1237–1240 (1994).
  CAS PubMed Google Scholar
• Groux, H. et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737–742 (1997).
  CAS PubMed Google Scholar
• Roncarolo, M. G. & Levings, M. K. The role of different subsets of T regulatory cells in controlling autoimmunity. Curr. Opin. Immunol. 12, 676–683 (2000).
  CAS PubMed Google Scholar
• Cottrez, F., Hurst, S. D., Coffman, R. L. & Groux, H. T regulatory cells 1 inhibit a TH2-specific response in vivo. J. Immunol. 165, 4848–4853 (2000).
  CAS PubMed Google Scholar
• Akdis, C. A., Blesken, T., Akdis, M., Wuthrich, B. & Blaser, K. Role of interleukin 10 in specific immunotherapy. J. Clin. Invest. 102, 98–106 (1998).
  CAS PubMed PubMed Central Google Scholar
• Pierkes, M. et al. Decreased release of histamine and sulfidoleukotrienes by human peripheral blood leukocytes after wasp venom immunotherapy is partially due to induction of IL-10 and IFN-γ production of T cells. J. Allergy Clin. Immunol. 103, 326–332 (1999).
  CAS PubMed Google Scholar
• Jilek, S., Barbey, C., Spertini, F. & Corthesy, B. Antigen-independent suppression of the allergic immune response to bee venom phospholipase A(2) by DNA vaccination in CBA/J mice. J. Immunol. 166, 3612–3621 (2001).
  CAS PubMed Google Scholar
• Zuany-Amorim, C. et al. Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice. J. Clin. Invest. 95, 2644–2651 (1995).
  CAS PubMed PubMed Central Google Scholar
• Stampfli, M. R. et al. Interleukin-10 gene transfer to the airway regulates allergic mucosal sensitization in mice. Am. J. Respir. Cell. Mol. Biol. 21, 586–596 (1999).
  CAS PubMed Google Scholar
• van den Biggelaar, A. H. et al. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 356, 1723–1727 (2000).
  CAS PubMed Google Scholar
• Oh, J. W. et al. CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation. J. Allergy Clin. Immunol. 110, 460–468 (2002).
  CAS PubMed Google Scholar
• Katagiri, K., Zhang-Hoover, J., Mo, J. S., Stein-Streilein, J. & Streilein, J. W. Using tolerance induced via the anterior chamber of the eye to inhibit TH2-dependent pulmonary pathology. J. Immunol. 169, 84–89 (2002).
  CAS PubMed Google Scholar
• Kosiewicz, M. M., Alard, P. & Streilein, J. W. Alterations in cytokine production following intraocular injection of soluble protein antigen: impairment in IFN-γ and induction of TGF-β and IL-4 production. J. Immunol. 161, 5382–5390 (1998).
  CAS PubMed Google Scholar
• D'Orazio, T. J. & Niederkorn, J. Y. A novel role for TGF-β and IL-10 in the induction of immune privilege. J. Immunol. 160, 2089–2098 (1998).
  CAS PubMed Google Scholar
• Kung, T. T. et al. Involvement of IL-5 in a murine model of allergic pulmonary inflammation: prophylactic and therapeutic effect of an anti-IL-5 antibody. Am. J. Respir. Cell. Mol. Biol. 13, 360–365 (1995).
  CAS PubMed Google Scholar
• Van Oosterhout, A. J. et al. Eosinophil infiltration precedes development of airway hyperreactivity and mucosal exudation after intranasal administration of interleukin-5 to mice. J. Allergy Clin. Immunol. 96, 104–112 (1995).
  CAS PubMed Google Scholar
• Foster, P. S., Hogan, S. P., Ramsay, A. J., Matthaei, K. I. & Young, I. G. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J. Exp. Med. 183, 195–201 (1996).
  CAS PubMed Google Scholar
• Lee, J. J. et al. Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma. J. Exp. Med. 185, 2143–2156 (1997).
  CAS PubMed PubMed Central Google Scholar
• Grunig, G. et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 282, 2261–2263 (1998).
  CAS PubMed PubMed Central Google Scholar
• Wills-Karp, M. et al. Interleukin-13: central mediator of allergic asthma. Science 282, 2258–2261 (1998).
  CAS PubMed Google Scholar
• Zhu, Z. et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J. Clin. Invest. 103, 779–788 (1999).
  CAS PubMed PubMed Central Google Scholar
• Walter, D. M. et al. Critical role for IL-13 in the development of allergen-induced airway hyperreactivity. J. Immunol. 167, 4668–4675 (2001).
  CAS PubMed Google Scholar
• Temann, U. A., Geba, G. P., Rankin, J. A. & Flavell, R. A. Expression of interleukin 9 in the lungs of transgenic mice causes airway inflammation, mast cell hyperplasia, and bronchial hyperresponsiveness. J. Exp. Med. 188, 1307–1320 (1998).
  CAS PubMed PubMed Central Google Scholar
• Townsend, J. M. et al. IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity 13, 573–583 (2000).
  CAS PubMed Google Scholar
• Temann, U. A., Ray, P. & Flavell, R. A. Pulmonary overexpression of IL-9 induces TH2 cytokine expression, leading to immune pathology. J. Clin. Invest. 109, 29–39 (2002).
  CAS PubMed PubMed Central Google Scholar
• McMillan, S. J., Bishop, B., Townsend, M. J., McKenzie, A. N. & Lloyd, C. M. The absence of interleukin 9 does not affect the development of allergen-induced pulmonary inflammation nor airway hyperreactivity. J. Exp. Med. 195, 51–57 (2002).
  CAS PubMed PubMed Central Google Scholar
• Whittaker, L. et al. Interleukin-13 mediates a fundamental pathway for airway epithelial mucus induced by CD4 T cells and interleukin-9. Am. J. Respir. Cell. Mol. Biol. 27, 593–602 (2002).
  CAS PubMed Google Scholar
• Kuperman, D. A. et al. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nature Med. 8, 885–889 (2002).
  CAS PubMed Google Scholar
• Postlethwaite, A. E. & Seyer, J. M. Fibroblast chemotaxis induction by human recombinant interleukin-4. Identification by synthetic peptide analysis of two chemotactic domains residing in amino acid sequences 70–88 and 89–122. J. Clin. Invest. 87, 2147–2152 (1991).
  CAS PubMed PubMed Central Google Scholar
• Postlethwaite, A. E., Holness, M. A., Katai, H. & Raghow, R. Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4. J. Clin. Invest. 90, 1479–1485 (1992).
  CAS PubMed PubMed Central Google Scholar
• Liu, X. et al. TH2 cytokine regulation of type I collagen gel contraction mediated by human lung mesenchymal cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 282, L1049–L1056 (2002).
  CAS PubMed Google Scholar
• Blease, K. et al. Therapeutic effect of IL-13 immunoneutralization during chronic experimental fungal asthma. J. Immunol. 166, 5219–5224 (2001).
  CAS PubMed Google Scholar
• Swain, S. L., Weinberg, A. D., English, M. & Huston, G. IL-4 directs the development of TH2-like helper effectors. J. Immunol. 145, 3796–3806 (1990).
  CAS PubMed Google Scholar
• Seder, R. A., Paul, W. E., Davis, M. M. & Fazekas de St Groth, B. The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice. J. Exp. Med. 176, 1091–1098 (1992).
  CAS PubMed Google Scholar
• Kopf, M. et al. Disruption of the murine IL-4 gene blocks TH2 cytokine responses. Nature 362, 245–248 (1993).
  CAS PubMed Google Scholar
• Fallon, P. G. et al. IL-4 induces characteristic TH2 responses even in the combined absence of IL-5, IL-9, and IL-13. Immunity 17, 7–17 (2002).
  CAS PubMed Google Scholar
• Barner, M., Mohrs, M., Brombacher, F. & Kopf, M. Differences between IL-4Rα-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of TH2 responses. Curr. Biol. 8, 669–672 (1998).
  CAS PubMed Google Scholar
• McKenzie, G. J. et al. Impaired development of TH2 cells in IL-13-deficient mice. Immunity 9, 423–432 (1998).
  CAS PubMed Google Scholar
• Urban, J. F. Jr et al. IL-13, IL-4Rα, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity 8, 255–264 (1998).
  CAS PubMed Google Scholar
• Finkelman, F. D. et al. IL-4 is required to generate and sustain in vivo IgE responses. J. Immunol. 141, 2335–2341 (1988).
  CAS PubMed Google Scholar
• Kuhn, R., Rajewsky, K. & Muller, W. Generation and analysis of interleukin-4 deficient mice. Science 254, 707–710 (1991).
  CAS PubMed Google Scholar
• Bonnefoy, J. Y., Gauchat, J. F., Lecoanet-Henchoz, S., Graber, P. & Aubry, J. P. Regulation of human IgE synthesis. Ann. NY Acad. Sci. 796, 59–71 (1996).
  CAS PubMed Google Scholar
• Emson, C. L., Bell, S. E., Jones, A., Wisden, W. & McKenzie, A. N. Interleukin (IL)-4-independent induction of immunoglobulin (Ig)E, and perturbation of T cell development in transgenic mice expressing IL-13. J. Exp. Med. 188, 399–404 (1998).
  CAS PubMed PubMed Central Google Scholar