title: The presence of small intestinal intraepithelial gamma/delta T-lymphocytes is inversely correlated with lymphoma development in refractory celiac disease.
abstract: 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).
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wieke H M
authors.initials: WH
authors.lastname: Verbeek
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: Petra E T
authors.initials: PE
authors.lastname: Scholten
authors.forename: D Joop
authors.initials: DJ
authors.lastname: Kuik
authors.forename: Chris J J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: Marco W J
authors.initials: MW
authors.lastname: Schreurs
mesh_terms: D000368:Aged; D002446:Celiac Disease / Q000150:complications / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology*; D008223:Lymphoma / Q000209:etiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta