Tetramer visualization of gut-homing gluten-specific T cells in the peripheral blood of celiac disease patients

Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2831-6. doi: 10.1073/pnas.0608610104. Epub 2007 Feb 16.

Abstract

Tetramers of MHC-peptide complexes are used for detection and characterization of antigen-specific T cell responses, but they require knowledge about both antigenic peptide and the MHC restriction element. The successful application of these reagents in human diseases involving CD4+ T cells is limited. Celiac disease, an intestinal inflammation driven by mucosal CD4+ T cells recognizing wheat gluten peptides in the context of disease-associated HLA-DQ molecules, is an ideal model to test the potential clinical use of these reagents. We investigated whether gluten-specific T cells can be detected in the peripheral blood of celiac disease patients using DQ2 tetramers. Nine DQ2+ patients and six control individuals on a gluten-free diet were recruited to the study. Participants consumed 160 g of gluten-containing bread daily for 3 days. After bread-challenge, gluten-specific T cells were detectable in the peripheral blood of celiac patients but not controls both directly by tetramer staining and indirectly by enzyme-linked immunospot. These T cells expressed the beta(7) integrin indicative of gut-homing properties. Most of the cells had a memory phenotype, but many other phenotypic markers showed a heterogeneous pattern. Tetramer staining of gluten-specific T cells has the potential to be used for diagnosis of celiac disease.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bread
  • Case-Control Studies
  • Celiac Disease / blood*
  • Celiac Disease / therapy
  • Cell Differentiation
  • Gastrointestinal Tract / immunology*
  • Glutens / immunology*
  • HLA-DQ Antigens / chemistry
  • HLA-DQ Antigens / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • Leukocytes, Mononuclear / immunology
  • Middle Aged
  • Phenotype
  • Protein Structure, Quaternary
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • Glutens
  • Interferon-gamma