Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia.

The pathogenesis of asthma remains unclear. An in vivo murine model of antigen-induced airway hyperreactivity and inflammation was developed to investigate the possibility, suggested by a wealth of descriptive human data, that alterations in immunoregulation are important in the genesis of airway hyperreactivity. A/J mice developed airway hyperreactivity and markedly increased numbers of pulmonary inflammatory cells following intraperitoneal sensitization and intratracheal challenge with sheep red blood cells. Notably, eosinophils were a prominent component of the inflammatory infiltrate. The dependence of these phenomena, both pathologic and functional, on CD4+ T lymphocytes was investigated by in vivo depletion of CD4+ cells using the anti-CD4 mAb GK1.5. When administered before antigen challenge, GK1.5 completely prevented both airway hyperreactivity and the infiltration of eosinophils. This model provides the first direct demonstration of the dependence of airway hyperreactivity upon CD4+ T lymphocytes, and the results are consistent with the possibility that eosinophils are effectors of this response.

[1]  I. van Ark,et al.  Effect of anti-IL-5 and IL-5 on airway hyperreactivity and eosinophils in guinea pigs. , 1993, The American review of respiratory disease.

[2]  D. Venzon,et al.  Changes in interleukin-2 and interleukin-4 production in asymptomatic, human immunodeficiency virus-seropositive individuals. , 1993, The Journal of clinical investigation.

[3]  S. Durham,et al.  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. , 1993, American journal of respiratory cell and molecular biology.

[4]  D. Laskin,et al.  Isolation and partial characterization of subpopulations of alveolar macrophages, granulocytes, and highly enriched interstitial macrophages from rat lung. , 1993, American journal of respiratory cell and molecular biology.

[5]  K. Takatsu,et al.  CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. , 1992, The American review of respiratory disease.

[6]  S. Durham,et al.  Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. , 1992, The American review of respiratory disease.

[7]  J. Virchow,et al.  Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. , 1992, The American review of respiratory disease.

[8]  P. W. Johnston,et al.  T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis. , 1992, The American review of respiratory disease.

[9]  S. Durham,et al.  Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. , 1992, The New England journal of medicine.

[10]  K. Weinberg,et al.  Defining protective responses to pathogens: cytokine profiles in leprosy lesions. , 1991, Science.

[11]  K. Blaser,et al.  Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. , 1991, The Journal of allergy and clinical immunology.

[12]  T. Suda,et al.  Analysis of the survival of mature human eosinophils: interleukin-5 prevents apoptosis in mature human eosinophils. , 1991, Blood.

[13]  C. Rochester,et al.  Is asthma T-cell mediated? , 1991, The American review of respiratory disease.

[14]  H. Jansen,et al.  Functional subsets of allergen-reactive human CD4+ T cells. , 1991, Immunology today.

[15]  G. Peltz.  A Role for CD4+ T‐Cell Subsets Producing a Selective Pattern of Lymphokines in the Pathogenesis of Human Chronic Inflammatory and Allergic Diseases , 1991, Immunological reviews.

[16]  H. van Loveren,et al.  T-cell-mediated induction of airway hyperreactivity in mice. , 1991, The American review of respiratory disease.

[17]  J. Curtis,et al.  Requirement of CD4-positive T cells for cellular recruitment to the lungs of mice in response to a particulate intratracheal antigen. , 1991, The Journal of clinical investigation.

[18]  F. Finkelman,et al.  Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. , 1991, Journal of immunology.

[19]  Roberta,et al.  Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. , 1991, The Journal of clinical investigation.

[20]  L. Allegra,et al.  Cellular and biochemical characteristics of bronchoalveolar lavage fluid in symptomatic nonallergic asthma. , 1991, The Journal of allergy and clinical immunology.

[21]  M. Schuyler,et al.  Dynamic T-cell changes in peripheral blood and bronchoalveolar lavage after antigen bronchoprovocation in asthmatics. , 1991, The American review of respiratory disease.

[22]  S. Durham,et al.  Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. , 1990, The American review of respiratory disease.

[23]  J. Bousquet,et al.  Eosinophilic inflammation in asthma. , 1990, The New England journal of medicine.

[24]  C. Corrigan,et al.  CD4 T-lymphocyte activation in acute severe asthma. Relationship to disease severity and atopic status. , 1990, The American review of respiratory disease.

[25]  J. Snapper.  Inflammation and airway function: the asthma syndrome. , 1990, The American review of respiratory disease.

[26]  G. Gleich.  The eosinophil and bronchial asthma: current understanding. , 1990, The Journal of allergy and clinical immunology.

[27]  A. Kay,et al.  T lymphocytes and eosinophils in allergen-induced late-phase asthmatic reactions in the guinea pig. , 1990, The American review of respiratory disease.

[28]  Ji Ming Wang,et al.  Recombinant human interleukin 5 is a selective eosinophil chemoattractant , 1989, European journal of immunology.

[29]  J. Curtis,et al.  Characterization of bronchoalveolar lymphocytes during a specific antibody-forming cell response in the lungs of mice. , 1989, The American review of respiratory disease.

[30]  W. Paul,et al.  IL-4 is required to generate and sustain in vivo IgE responses. , 1988, Journal of immunology.

[31]  D. Hendrick,et al.  Number and activity of inflammatory cells in bronchoalveolar lavage fluid in asthma and their relation to airway responsiveness. , 1988, Thorax.

[32]  W. Mitzner,et al.  Expression of airway hyperreactivity to acetylcholine as a simple autosomal recessive trait in mice , 1988, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  C. Corrigan,et al.  T LYMPHOCYTE ACTIVATION IN ACUTE SEVERE ASTHMA , 1988, The Lancet.

[34]  T. Suda,et al.  Highly purified murine interleukin 5 (IL-5) stimulates eosinophil function and prolongs in vitro survival. IL-5 as an eosinophil chemotactic factor , 1988, The Journal of experimental medicine.

[35]  W. Seaman,et al.  Induction of immune tolerance during administration of monoclonal antibody to L3T4 does not depend on depletion of L3T4+ cells. , 1988, Journal of immunology.

[36]  J. Gamble,et al.  Recombinant human interleukin 5 is a selective activator of human eosinophil function , 1988, The Journal of experimental medicine.

[37]  A. Wardlaw,et al.  Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma. Relationship to bronchial hyperreactivity. , 1988, The American review of respiratory disease.

[38]  I. G. Young,et al.  Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5). , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[39]  P. Moseley,et al.  Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Description of the model and local airway inflammation. , 1987, The American review of respiratory disease.

[40]  D. Wofsy,et al.  Administration of F(ab')2 fragments of monoclonal antibody to L3T4 inhibits humoral immunity in mice without depleting L3T4+ cells. , 1986, Journal of immunology.

[41]  R. Coffman,et al.  Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. , 1986, Journal of immunology.

[42]  F. Finkelman,et al.  IgD-secreting murine plasmacytomas: identification and partial characterization of two IgD myeloma proteins. , 1981, Journal of immunology.