title: Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma.
abstract: BACKGROUND
  Asthma is characterized by a T(H)2 immune response. CD4(+)CD25(hi) regulatory T cells (Tregs) have been proposed to prevent allergic diseases through suppression of T(H)2 responses.
  
  
  OBJECTIVE
  We sought to investigate the role of CD4(+)CD25(hi) T cells in children with asthma.
  
  
  METHODS
  CD4(+)CD25(hi) Tregs and forkhead/winged-helix transcription factor FOXP3 mRNA levels were quantified in peripheral blood and bronchoalveolar lavage fluid (BALF) of 18 children with asthma, 10 children with chronic cough, and 13 control subjects without lung diseases. CD4(+)CD25(hi) T cells were isolated from peripheral blood and BALF of asthmatic patients and control subjects, and their capacity to suppress proliferation and cytokine/chemokine production of autologous responder T cells was analyzed.
  
  
  RESULTS
  CD4(+)CD25(hi) T cells were decreased in BALF of asthmatic children compared with values in children with cough or control subjects. In children with asthma, inhaled corticosteroid treatment was associated with increased percentages of CD4(+)CD25(hi) T cells in peripheral blood and BALF. Isolated BALF and peripheral blood CD4(+)CD25(hi) T cells from nonasthmatic subjects suppressed proliferation and cytokine/chemokine production by CD4(+)CD25(-) responder T cells. BALF CD4(+)CD25(hi) T cells from asthmatic subjects failed to suppress proliferation and production of T(H)2-associated cytokines and chemokines by CD4(+)CD25(-) responder T cells, which was restored after use of inhaled corticosteroids.
  
  
  CONCLUSIONS
  These findings provide the first evidence that pulmonary CD4(+)CD25(hi) Tregs are impaired in pediatric asthma.
  
  
  CONCLUSIONS
  Pulmonary Tregs might represent a therapeutic target in pediatric asthma.
authors.affiliation: Children's Hospital of the Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
authors.forename: Barbara
authors.initials: B
authors.lastname: Koller
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Mehlhorn
authors.forename: Dietrich
authors.initials: D
authors.lastname: Reinhardt
authors.forename: Thomas
authors.initials: T
authors.lastname: Nicolai
authors.forename: Dolores J
authors.initials: DJ
authors.lastname: Schendel
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.forename: Susanne
authors.initials: S
authors.lastname: Krauss-Etschmann
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008168:Lung / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger