title: Up-regulated cytokine-inducible SH2-containing protein expression in allergen-stimulated T cells from hen's egg-allergic patients.
abstract: BACKGROUND
  Although changes in the fine balance of allergen-specific T cells are crucial in the pathogenesis of allergic diseases, their roles in the allergic reaction to hen's eggs (HE) have not yet been fully analysed.
  
  
  OBJECTIVE
  Using microarray technology, allergen-stimulated T cells from HE-allergic children were analysed to identify genes that are specifically up-regulated in these cells.
  
  
  METHODS
  RNA from CD4(+) CD14(-) cells, fractionated from allergen-stimulated peripheral mononuclear cells, was analysed using a whole-genome microarray and real-time RT-PCR. The protein expression of selected genes was ascertained by flow cytometry.
  
  
  RESULTS
  In microarray analyses of allergen-stimulated T cells, 43 genes were up-regulated in HE-allergic children but not in non-HE-allergic children. Among these, up-regulation of three genes, cytokine -inducible SH2-containing protein (CISH), nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor Z (NFKBIZ) and B-cell CLL/lymphoma 2 (BCL2), was confirmed by real-time quantitative RT-PCR. CISH, but not NFKBIZ or BCL2, showed a significantly higher ratio of antigen-stimulated cell transcription over unstimulated cells in HE-allergic than in non-HE-allergic children (P<0.01). Flow-cytometric analysis revealed that the percentage of CD25(+)CISH(+) cells in CD4(+) cells from patients with HE allergy was significantly higher than that in controls (P<0.01). The expression level of CISH was significantly higher in IL-4(+) Th2 cells than in IFN-gamma(+) Th1 cells.
  
  
  CONCLUSIONS
  We noted that CISH expression in allergen-stimulated CD4(+) T cells from HE-allergic patients was significantly increased in both mRNA and protein levels compared with that from non-HE-allergic children.
authors.affiliation: Department of Pediatrics, School of Medicine, Fujita Health University, Aichi-Ken, Japan. ynakaji@fujita-hu.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Nakajima
authors.forename: I
authors.initials: I
authors.lastname: Tsuge
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
authors.forename: R
authors.initials: R
authors.lastname: Komatsubara
authors.forename: N
authors.initials: N
authors.lastname: Hirata
authors.forename: M
authors.initials: M
authors.lastname: Kakami
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Kurahashi
authors.forename: A
authors.initials: A
authors.lastname: Urisu
authors.forename: Y
authors.initials: Y
authors.lastname: Asano
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000485:Allergens / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002645:Chickens; D002675:Child, Preschool; D021181:Egg Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins; D007223:Infant; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D015854:Up-Regulation; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000485:Allergens; D020672:I-kappa B Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D050826:Suppressor of Cytokine Signaling Proteins; C417234:NFKBIZ protein, human