Expansion of CD8+ T cells with regulatory function after interaction with intestinal epithelial cells

Gastroenterology. 2002 Nov;123(5):1516-26. doi: 10.1053/gast.2002.36588.


Background & aims: Regulatory T cells play a role in the control of immune responses in the intestinal mucosa and their absence may predispose to inflammatory bowel disease (IBD). We have previously shown that T cells activated by intestinal epithelial cells (IECs) are suppressive in function. Our goal was to characterize the phenotype and function of T cells proliferating after interaction with IECs.

Methods: Irradiated human IECs, isolated from normal resection specimens, were cultured with carboxy fluorescein succinimidyl ester (CFSE) labeled T cells. Flow cytometric analysis of T cells was performed at days 5-10. CD8+ T cells proliferating in culture with IECs were sorted and added to suppressive assays.

Results: The precursor frequency of T cells proliferating in response to IECs ranged from 0.3%-0.9%. Several subpopulations were shown to proliferate (CD8+CD28-/CD8+CD28+/CD4+CD25+), but one population (CD8+CD28-CD101+CD103+) appeared to be dependent on contact with the CD8 ligand gp180. After sorting, culture in the presence of interleukin (IL)-7 and IL-15 allowed for the generation of cell lines. IEC-activated CD8+ T cells, but not nonactivated CD8+ T cells, were suppressive in function. Suppression belonged to the CD101+CD103+ subset of IEC-activated CD8+ T cells and appeared to require cell contact. CD8+ lamina propria T cells also showed suppressive function, suggesting the presence of CD8+ regulatory T cells in the mucosa.

Conclusions: IECs are able to induce the proliferation of a small fraction of CD8+ peripheral T cells. The CD8+CD28- subset of IEC-activated CD8+ T cells, which express CD101 and CD103, interacts with IECs through gp180 and has regulatory function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / metabolism
  • Biomarkers
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Communication / physiology*
  • Cell Division / physiology
  • Cells, Cultured
  • Coculture Techniques
  • Humans
  • Integrin alpha Chains / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / physiology*
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / physiology
  • Phenotype
  • T-Lymphocyte Subsets / cytology


  • Antigens, CD
  • Biomarkers
  • CD101 antigen, human
  • Integrin alpha Chains
  • Membrane Glycoproteins
  • alpha E integrins
  • elastin microfibril interface located protein