Impaired secretion of interleukin-4 and interleukin-13 by allergen-specific T cells correlates with defective nuclear expression of NF-AT2 and jun B: relevance to immunotherapy

Clin Exp Allergy. 2003 Sep;33(9):1209-15. doi: 10.1046/j.1365-2222.2003.01748.x.

Abstract

Background: Allergen immunotherapy (IT) is a successful treatment associated with decreased Th2 cytokine production by allergen-specific T cells. We have previously demonstrated (Faith et al., J Immunol 1997; 159:53-57) that inhibition of Th2 cytokine production in vitro correlates with impaired tyrosine kinase activity through the TCR. The transcription factor complex, nuclear factor of activated T cells (NF-AT), which regulates Th2 cytokine production is controlled by the activity of tyrosine kinases.

Objective: To address whether decreased Th2 cytokine production by allergen-specific CD4+ T cells following IT is correlated with altered translocation and nuclear expression of the NF-AT family member, NF-AT2, and the activator protein 1 (AP1) component of NF-AT, jun B.

Methods: T cell lines specific for insect venom phospholipase A2 (PLA) were derived from patients prior to and during conventional venom IT. Nuclear expressions of NF-AT and jun B were assessed following stimulation through the TCR. Th1 and Th2 cytokine and IL-10 production by insect venom-specific T cells were also determined. Results were compared with a well-established model system in which anergy was induced in cloned, allergen-specific Th2 cells.

Results: Impaired translocation and decreased expression of NF-AT2 and jun B were detected in PLA-specific T cell lines derived from bee venom-allergic individuals following 16 weeks treatment compared to pre-treatment. These results correlated with significantly reduced production of IL-4 and IL-13 and significantly increased production of IFN-gamma and IL-10 by PLA-specific T cells. Impaired IL-4 and IL-13 production also correlated with defective nuclear expression of NF-AT2/jun B in cloned, anergic allergen-specific Th2 cells.

Conclusion: These results suggested that optimal production of IL-4 and IL-13 by allergen-specific T cells is dependent on the nuclear expression of NF-AT2 and jun B. Thus, specific inhibition of NF-AT2/jun B might be an option in novel and improved forms of allergen IT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Bee Venoms / immunology
  • Cell Line
  • Cell Nucleus / immunology
  • DNA-Binding Proteins / genetics
  • Enzyme-Linked Immunosorbent Assay / methods
  • Humans
  • Immunotherapy / methods*
  • Interferon-gamma / biosynthesis
  • Interleukin-13 / biosynthesis*
  • Interleukin-13 / immunology
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / immunology
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Phospholipases A / immunology
  • Phospholipases A2
  • Proto-Oncogene Proteins c-jun / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Th2 Cells / immunology*
  • Transcription Factor AP-1 / genetics
  • Transcription Factors / genetics*
  • Translocation, Genetic / genetics
  • Wasp Venoms / immunology

Substances

  • Allergens
  • Bee Venoms
  • DNA-Binding Proteins
  • Interleukin-13
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-jun
  • Receptors, Antigen, T-Cell
  • Transcription Factor AP-1
  • Transcription Factors
  • Wasp Venoms
  • Interleukin-4
  • Interferon-gamma
  • Phospholipases A
  • Phospholipases A2