title: Origin and immunophenotype of aberrant IEL in RCDII patients.
abstract: OBJECTIVE
  Aberrant intra-epithelial lymphocytes (IELs) are the hallmark of refractory coeliac disease type II RCDII and considered a premalignant cell population from which aggressive enteropathy-associated T cell lymphoma (EATL) can evolve. The aim of this study was to gain further insight in the origin and characteristics of aberrant IELs by analysing T-cell receptor (TCR) rearrangements, and by immunophenotypic analysis of aberrant IELs.
  
  
  METHODS
  Duodenal biopsies from 18 RCDII patients and three RCDII cell lines were analysed for the presence of TCR delta, gamma, and beta rearrangements. In addition, IELs isolated from biopsies derived from RCDII patients were phenotypically analysed.
  
  
  RESULTS
  Aberrant IELs showed an upregulated expression of granzyme B and decreased expression of PCNA. TCR rearrangements in the aberrant IEL population in biopsies of RCDII patients were heterogenic, which is most likely due to a variation in maturity. Similarly, RCDII cell lines displayed a heterogenic TCR rearrangement pattern.
  
  
  CONCLUSIONS
  Aberrant IELs originate from deranged immature T lymphocytes and display clear differentiation to a cytotoxic phenotype. Aberrant IELs displayed different stages of maturity between RCDII patients, of which only the patients harbouring the most mature aberrant IEL population developed an EATL.
authors.affiliation: Gastroenterology and Hepatology, VU University Medical Center, The Netherlands. g.tack@vumc.nl
authors.forename: Greetje J
authors.initials: GJ
authors.lastname: Tack
authors.forename: Roy L J
authors.initials: RL
authors.lastname: van Wanrooij
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Jennifer M L
authors.initials: JM
authors.lastname: Tjon
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: Danielle A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Bergen
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
authors.forename: Gerd
authors.initials: G
authors.lastname: Bouma
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; D015139:Blotting, Southern; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D020349:Surface Plasmon Resonance
chemical_list: D011948:Receptors, Antigen, T-Cell