Activated T lymphocytes in the celiac lesion: non-proliferative activation (CD25) of CD4+ alpha/beta cells in the lamina propria but proliferation (Ki-67) of alpha/beta and gamma/delta cells in the epithelium

Eur J Immunol. 1993 Feb;23(2):505-10. doi: 10.1002/eji.1830230231.


In order to identify any dominating subset of activated T cells in the celiac lesion, we examined CD3+, CD4+, CD8+ and T cell receptor (TcR) gamma/delta+ lymphocytes in jejunal cryosections from 25 patients with celiac disease and 10 controls by three-color immunofluorescence staining for expression of the nuclear proliferation marker detected by monoclonal antibody (mAb) Ki-67 and the p55 alpha chain of interleukin-2 receptor (CD25). mAb Ki-67+ intraepithelial lymphocytes (IEL) were exclusively observed in celiac patients. The median proportion of CD3+ IEL positive for Ki-67 increased from nil in controls to 4.5% in partly treated (range 0-19.0%; n = 10; p = < 0.05) and 12.8% in untreated celiac disease (range 4.0-30.7%; n = 15; p < 0.005). Only 1.5% of CD3+ subepithelial T cells expressed the Ki-67 marker in celiac disease (range 0-9.5%). Two- and three-color staining combining mAb to CD3 and Ki-67 with mAb to CD4, CD8 or TcR delta showed that both TcR alpha/beta+ CD8+ and TcR gamma/delta+ (but not CD4+) mucosal T cells proliferated in the epithelium. By contrast, CD25 were almost exclusively expressed on CD4+ T cells in the lamina propria. The percentage of CD25+ T cells increased significantly from 1.7% in controls (range 0-2.9%) to 7.5% in partly treated (range 0.8-17.8%, p < 0.002), and to 14.65% in untreated celiac disease (range 3.9-21%, p < 0.002). These results suggest that gluten ingestion in celiac disease induces proliferative activation of TcR alpha/beta+ CD8+ and TcR gamma/delta+ IEL but non-proliferative activation (lymphokine production?) of lamina propria CD4+ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Celiac Disease / immunology*
  • Celiac Disease / pathology
  • Child
  • Child, Preschool
  • Epithelium / immunology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Immunophenotyping
  • Infant
  • Intestinal Mucosa / immunology*
  • Ki-67 Antigen
  • Lymphocyte Activation / immunology*
  • Middle Aged
  • Neoplasm Proteins / immunology*
  • Nuclear Proteins / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Interleukin-2 / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology


  • Antibodies, Monoclonal
  • CD3 Complex
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin-2