Airway epithelial cell-derived insulin-like growth factor-1 triggers skewed CD8(+) T cell polarization

Cell Biol Int. 2014 Oct;38(10):1148-54. doi: 10.1002/cbin.10313. Epub 2014 Jul 16.

Abstract

Skewed CD8(+) T cell responses are important in airway inflammation. This study investigates the role of the airway epithelial cell-derived insulin-like growth factor 1 (IGF1) in contributing to CD8(+) T cell polarization. Expression of IGF1 in the airway epithelial cell line, RPMI2650 cells, was assessed by quantitative real time RT-PCR and Western blotting. The role of IGF1 in regulating CD8(+) T cell activation was observed by coculture of mite allergen-primed RPMI2650 cells and naïve CD8(+) T cells. CD8(+) T cell polarization was assessed by the carboxyfluorescein succinimidyl ester-dilution assay and the determination of cytotoxic cytokine levels in the culture medium. Exposure to mite allergen, Der p1, increased the expression of IGF1 by RPMI2650 cells. The epithelial cell-derived IGF1 prevented the activation-induced cell death by inducing the p53 gene hypermethylation. Mite allergen-primed RPMI2650 cells induced an antigen-specific CD8(+) T cell polarization. We conclude that mite allergens induce airway epithelial cell line, RPMI2650 cells, to produce IGF1; the latter contributes to antigen-specific CD8(+) T cell polarization.

Keywords: CD8 T cells; P53 gene methylation; airway; epithelial cells; insulin-like growth factor-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Dermatophagoides / pharmacology
  • Arthropod Proteins / pharmacology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects*
  • Cysteine Endopeptidases / pharmacology
  • DNA Methylation / drug effects
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Insulin-Like Growth Factor I / isolation & purification
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • MAP Kinase Kinase Kinases / metabolism
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation / drug effects

Substances

  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Tumor Suppressor Protein p53
  • Insulin-Like Growth Factor I
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase Kinases
  • Cysteine Endopeptidases
  • Dermatophagoides pteronyssinus antigen p 1