The presence of small intestinal intraepithelial gamma/delta T-lymphocytes is inversely correlated with lymphoma development in refractory celiac disease

Am J Gastroenterol. 2008 Dec;103(12):3152-8. doi: 10.1111/j.1572-0241.2008.02213.x.


Background: In refractory celiac disease (RCD) type II, a phenotypically aberrant (CD7+ CD3- CD4/8-cytoplasmicCD3+) intraepithelial lymphocyte (IEL) population is present, and 50-60% of these patients develop enteropathy-associated T-cell lymphoma (EATL). TCRgammadelta+ IELs play an important role in mucosal repair, homeostasis, and tumor surveillance. Recently, human small intestinal TCRgammadelta+ IELs were shown to have regulatory potential in uncomplicated celiac disease (CD).

Aim: In the present study, we investigated whether TCRgammadelta+ IELs are decreased in RCD II, providing a possible explanation for persisting mucosal damage and inflammation, and the emergence of aberrant T cells with clonal expansion to EATL.

Design and methods: Multiparameter flow cytometric immunophenotyping was performed on IELs isolated from fresh small bowel biopsy specimens of relatively large distinct CD patient and control groups (N = 87).

Results: A significantly lower percentage of TCRgammadelta+ IELs was found in RCD II as compared to all other CD groups. In contrast, in uncomplicated CD patients significantly more TCRgammadelta+ IELs were found than in controls. Overall, there is a clear negative relation between TCRgammadelta+ IELs and aberrant IELs. Interestingly, TCRgammadelta+ IELs increase again in RCD II after effective therapy.

Conclusions: The observed negative relation between TCRgammadelta+ and aberrant IELs, along with their known regulatory capacity in uncomplicated CD, implies that TCRgammadelta+ IELs may play a crucial role in mucosal repair, regaining homeostasis and possibly even tumor surveillance. These cells may be important markers, in addition to the aberrant T cells, to differentiate between disease categories and to evaluate the effectiveness of therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Celiac Disease / complications
  • Celiac Disease / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Intestinal Mucosa / immunology
  • Intestine, Small / immunology*
  • Lymphoma / etiology
  • Lymphoma / immunology*
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocytes / immunology*


  • Receptors, Antigen, T-Cell, gamma-delta