Up-regulated cytokine-inducible SH2-containing protein expression in allergen-stimulated T cells from hen's egg-allergic patients

Clin Exp Allergy. 2008 Sep;38(9):1499-506. doi: 10.1111/j.1365-2222.2008.03030.x. Epub 2008 Jul 19.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Allergens / immunology*
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Chickens
  • Child, Preschool
  • Egg Hypersensitivity / immunology
  • Egg Hypersensitivity / metabolism*
  • Female
  • Humans
  • I-kappa B Proteins
  • Infant
  • Male
  • Nuclear Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Up-Regulation
  • src Homology Domains*

Substances

  • Adaptor Proteins, Signal Transducing
  • Allergens
  • I-kappa B Proteins
  • NFKBIZ protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Suppressor of Cytokine Signaling Proteins
  • cytokine inducible SH2-containing protein