title: CD4-mediated regulatory T-cell activation inhibits the development of disease in a humanized mouse model of allergic airway disease.
abstract: BACKGROUND
  Based on their potency to control allergic diseases, regulatory T (Treg) cells represent a promising target for novel strategies to interfere with allergic airway inflammation. We have previously demonstrated that stimulation of the CD4 molecule on human Treg cells activates their suppressive activity in vitro and in vivo.
  
  
  OBJECTIVE
  We sought to determine the effect of CD4-mediated Treg-cell activation on pulmonary inflammation in a humanized mouse model of allergic airway inflammation.
  
  
  METHODS
  PBMCs obtained from donors allergic to birch pollen or from healthy donors were injected into NOD-severe combined immunodeficiency γc(-/-) mice, followed by allergen airway challenges and analysis of airway responsiveness and inflammation. For Treg-cell activation, mice were treated with the CD4-binding, lck-activating recombinant HIV-1 surface protein gp120 after sensitization prior to allergen challenge. Control experiments with CD25-depleted PBMCs were performed to evaluate the role of Treg cells.
  
  
  RESULTS
  PBMCs from allergic donors but not from healthy donors induced airway inflammation and airway hyperresponsiveness. Treatment with gp120 prior to allergen challenge abrogated airway hyperresponsiveness and reduced the inflammatory immune response. In contrast, treatment had no effect on inflammation and airway hyperresponsiveness in mice that received CD25-depleted PBMCs, demonstrating Treg-cell dependency of disease prevention.
  
  
  CONCLUSIONS
  Allergic airway inflammation can be prevented by stimulation of human Treg cells by CD4. These results suggest a clinical potential of Treg-cell activation by high-affinity CD4 ligands in allergic diseases.
authors.affiliation: III Medical Department, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Helen
authors.initials: H
authors.lastname: Martin
authors.forename: Sebastian
authors.initials: S
authors.lastname: Reuter
authors.forename: Nina
authors.initials: N
authors.lastname: Dehzad
authors.forename: Anke
authors.initials: A
authors.lastname: Heinz
authors.forename: Iris
authors.initials: I
authors.lastname: Bellinghausen
authors.forename: Joachim
authors.initials: J
authors.lastname: Saloga
authors.forename: Ina
authors.initials: I
authors.lastname: Haasler
authors.forename: Stephanie
authors.initials: S
authors.lastname: Korn
authors.forename: Helmut
authors.initials: H
authors.lastname: Jonuleit
authors.forename: Roland
authors.initials: R
authors.lastname: Buhl
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
mesh_terms: D000328:Adult; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology; D015704:CD4 Antigens / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D015847:Interleukin-4