Profoundly Expanded T-cell Clones in the Inflamed and Uninflamed Intestine of Patients With Crohn's Disease

J Crohns Colitis. 2017 Jul 1;11(7):831-839. doi: 10.1093/ecco-jcc/jjx012.


Background and aim: T cells are key players in the chronic intestinal inflammation that characterises Crohn's disease. Here we aim to map the intestinal T-cell receptor [TCR] repertoire in patients with Crohn's disease, using next-generation sequencing technology to examine the clonality of the T-cell compartment in relation to mucosal inflammation and response to therapy.

Methods: Biopsies were taken from endoscopically inflamed and uninflamed ileum and colon of 19 patients with Crohn's disease. From this cohort, additional biopsies were taken after 8 weeks of remission induction therapy from eight responders and eight non-responders. Control biopsies from 11 patients without inflammatory bowel disease [IBD] were included. The TCRβ repertoire was analysed by next-generation sequencing of biopsy RNA.

Results: Both in Crohn's disease patients and in non-IBD controls, a broad intestinal T-cell repertoire was found, with a considerable part consisting of expanded clones. Clones in Crohn's disease were more expanded [p = 0.008], with the largest clones representing up to as much as 58% of the total repertoire. There was a substantial overlap of the repertoire between inflamed and uninflamed tissue and between ileum and colon. Following therapy, responders showed larger changes in the T-cell repertoire than non-responders, although a considerable part of the repertoire remained unchanged in both groups.

Conclusions: The intestinal T-cell repertoire distribution in Crohn's disease is different from that in the normal gut, containing profoundly expanded T-cell clones that take up a large part of the repertoire. The T-cell repertoire is fairly stable regardless of endoscopic mucosal inflammation or response to therapy.

Keywords: Crohn’s disease; TCR; next-generation sequencing.

MeSH terms

  • Adalimumab / therapeutic use
  • Adult
  • Anti-Inflammatory Agents / therapeutic use
  • Biopsy
  • Budesonide / therapeutic use
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Clone Cells / drug effects
  • Colon / pathology
  • Crohn Disease / drug therapy
  • Crohn Disease / immunology*
  • Crohn Disease / pathology*
  • Female
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Ileum / pathology
  • Inflammation / immunology
  • Inflammation / pathology
  • Infliximab / therapeutic use
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell / metabolism*
  • Severity of Illness Index
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology*
  • Young Adult


  • Anti-Inflammatory Agents
  • Gastrointestinal Agents
  • Receptors, Antigen, T-Cell
  • Budesonide
  • C-Reactive Protein
  • Infliximab
  • Adalimumab