title: Impaired Ca²⁺ regulation of CD4⁺CD25⁺ regulatory T cells from pediatric asthma.
abstract: BACKGROUND
  CD4(+)CD25(+) regulatory T (T(reg)) cells can control the allergic response to allergen, airway eosinophilia and airway hypersensitivity. We speculated that chronic inflammation persisting in asthma airways is dependent on abnormalities of these T(reg) cells. There are differences in the pathology of asthma in adults and children, and the airways of pediatric asthma are considered to be more naive than those of adults. Therefore, we analyzed the functionality of T(reg) cells in pediatric asthma and the relationship between T(reg) function and asthma symptoms.
  
  
  METHODS
  The anergic state, which is one of the defining properties of T(reg), was analyzed by measuring intracellular Ca(2+) influx following T cell receptor (TCR) stimulation. FOXP3-positive cells and FOXP3 mRNA expression were measured by flow analysis and real-time PCR with the SYBR method, respectively.
  
  
  RESULTS
  CD45RO(+) cells make up approximately 99% of CD4(+)CD25(high) T cells and 89% of CD4(+)CD25(low) T cells in human adult blood. The proportion of CD45RO(+) cells in CD4(+)CD25(+) (high + low) T cells from pediatric asthma was much smaller (about 56%). Interestingly, our data indicated that CD45RO(+) T(reg) cells from pediatric asthma aberrantly increased intracellular Ca(2+) concentrations following TCR activation compared with pediatric nonasthma controls.
  
  
  CONCLUSIONS
  These impaired CD45RO(+) T(reg) cell functions were correlated with asthma symptoms. The correlation was observed in the group with a highly expressed atopic phenotype and longer duration of asthma. We suggest that chronic inflammation in pediatric asthma airways may be the result of impaired regulatory functions of CD45RO(+) T(reg) cells.
authors.affiliation: Department of Paediatrics, Tokyo Metropolitan Ebara Hospital, Tokyo, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Takaharu
authors.initials: T
authors.lastname: Negoro
authors.forename: Akane
authors.initials: A
authors.lastname: Hoshi
authors.forename: Akiko
authors.initials: A
authors.lastname: Wakagi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Alison H
authors.initials: AH
authors.lastname: Banham
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishii
authors.forename: Haruyo
authors.initials: H
authors.lastname: Akiyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kiuchi
authors.forename: Susumu
authors.initials: S
authors.lastname: Sunaga
authors.forename: Takashi
authors.initials: T
authors.lastname: Tobe
authors.forename: Giovanna
authors.initials: G
authors.lastname: Roncador
authors.forename: Kazuo
authors.initials: K
authors.lastname: Itabashi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakano
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000276:immunology*; D002118:Calcium / Q000276:immunology*; D002648:Child; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008297:Male; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D017493:Leukocyte Common Antigens; D002118:Calcium