title: Susceptibility to allergic lung disease regulated by recall responses of dual-receptor memory T cells.
abstract: BACKGROUND
  Microbial infections are associated with the initial susceptibility to and flares of asthma. However, immunologic mechanisms whereby infections might alter the asthmatic phenotype are lacking.
  
  
  OBJECTIVE
  To test the hypothesis that memory T cells specific both for a viral antigen and an allergen could influence the pathogenesis of allergic disease in vivo .
  
  
  METHODS
  We developed a system in which 2 distinct T-cell receptors coexist on the T-cell surface, 1 specific for a virus and the other for an inhaled antigen.
  
  
  RESULTS
  We show that a population of dual-receptor T cells, polarized through a virus-specific T-cell receptor to contain T(H)1 or T(H)2 cells, can be reactivated through an unrelated T-cell receptor in recall responses in vivo . Quiescent memory cells derived from a T(H)1-polarized effector population blocked the development of airway hyperreactivity in a model of allergic lung disease, in association with decreased induction of chemokines and eosinophil recruitment. Conversely, reactivation of quiescent T(H)2 cells after inhalation of antigen or virus infection was sufficient to lead to the development of airway hyperresponsiveness and allergic pulmonary inflammation in mice whose lungs were previously normal.
  
  
  CONCLUSIONS
  These data provide evidence that dual-receptor memory T cells can regulate allergic disease susceptibility and suggest that they may play a role in mediating the influence of microbes on asthma pathogenesis.
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH 44195, USA. aronicm@ccf.org
authors.forename: Mark A
authors.initials: MA
authors.lastname: Aronica
authors.forename: Shadi
authors.initials: S
authors.lastname: Swaidani
authors.forename: Yan H
authors.initials: YH
authors.lastname: Zhang
authors.forename: Daphne
authors.initials: D
authors.lastname: Mitchell
authors.forename: Ana L
authors.initials: AL
authors.lastname: Mora
authors.forename: Susan
authors.initials: S
authors.lastname: McCarthy
authors.forename: Jamye
authors.initials: J
authors.lastname: O'Neal
authors.forename: David
authors.initials: D
authors.lastname: Topham
authors.forename: James R
authors.initials: JR
authors.lastname: Sheller
authors.forename: Mark
authors.initials: M
authors.lastname: Boothby
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D006967:Hypersensitivity / Q000209:etiology* / Q000276:immunology; D007156:Immunologic Memory; D008171:Lung Diseases / Q000209:etiology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell