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Mol Immunol. 2012 Apr;50(4):262-70. doi: 10.1016/j.molimm.2012.01.014. Epub 2012 Feb 23.

Origin and immunophenotype of aberrant IEL in RCDII patients.

Author information

  • 1Gastroenterology and Hepatology, VU University Medical Center, The Netherlands. g.tack@vumc.nl

Abstract

OBJECTIVES:

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.

DESIGN:

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.

CONCLUSION:

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.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID:
22364936
[PubMed - indexed for MEDLINE]
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