Majority of gliadin-specific T-cell clones from celiac small intestinal mucosa produce interferon-gamma and interleukin-4

Dig Dis Sci. 1998 Jan;43(1):156-61. doi: 10.1023/a:1018896625699.

Abstract

An abnormal mucosal cell-mediated immune response plays a fundamental role in the pathogenesis of celiac disease. To characterize locally infiltrating T cells, gliadin-specific T-cell clones were isolated from two treated celiac patients. Mucosal biopsies were cultured in vitro for 24 hr with a peptic-tryptic digest (PT) of gliadin. T-cell clones (TCC) were then isolated by limiting dilution. The production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was evaluated by ELISA in culture supernatants obtained after a short incubation with anti-CD3 and PMA, or with antigen. Twenty-two TCC were specific for gliadin and/or PT. All were CD3+, CD4+, CD8-, TCR alphabeta+. In one such clone the PT-specific response was inhibited by an anti-DQ, but not by an anti-DR antibody. Of the five gliadin-specific TCC examined, four produced IL-4 and high levels of IFN-gamma; the remaining one initially produced only IL-4, but subsequently also IFN-gamma. All clones obtained from the celiac mucosa, including the gliadin-specific ones, produced high levels of IFN-gamma, in most cases with IL-4. This cytokine profile could explain most of the immunological features of the celiac mucosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibody Specificity
  • Celiac Disease / immunology*
  • Clone Cells
  • Female
  • Gliadin / immunology*
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / biosynthesis*
  • Interleukin-4 / biosynthesis*
  • Intestinal Mucosa / immunology*
  • Intestine, Small / immunology*
  • Male
  • T-Lymphocytes / immunology*

Substances

  • Interleukin-4
  • Interferon-gamma
  • Gliadin