Uptake and presentation of antigen to T cells by primary colonic epithelial cells in normal and diseased states

Gastroenterology. 2000 Dec;119(6):1548-59. doi: 10.1053/gast.2000.20168.

Abstract

Background & aims: The immunoregulatory properties of primary colonic epithelial cells (CECs) have not been defined. The ability of CECs from wild-type and interleukin 2-deficient (IL-2(-/-)) mice to take up a complex protein antigen and present peptides via MHC molecules to T cells was assessed and contrasted with that of primary small intestinal epithelial cells (SIECs).

Methods: Uptake of fluorescein isothiocyanate (FITC)-labeled ovalbumin (FITC-OVA) by CECs and SIECs from wild-type and IL-2(-/-) mice was measured by flow cytometry. The effect of disrupting cytoskeleton organization and metabolic activity of CEC on antigen uptake was assessed. An OVA/I-A(b)-specific CD4(+) T-cell line transfected with an NFAT-lacZ reporter gene construct was used to evaluate the ability of CECs and SIECs as well as CECs from healthy and colitic IL-2(-/-) mice to present antigen to T cells.

Results: Uptake of FITC-OVA by CECs is concentration dependent, is not saturated at physiologic concentrations, and requires metabolically active cells. CECs from IL-2(-/-) mice take up significantly more antigen than those from wild-type mice. CECs are more efficient APCs than SIECs, and antigen-pulsed CECs from IL-2(-/-) mice induce the highest levels of T-cell activation.

Conclusions: Primary CECs are efficient APCs for CD4 MHC class II-restricted T cells. Antigen uptake and presentation is up-regulated in animals prone to develop intestinal inflammation.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / metabolism*
  • Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Line
  • Colitis / metabolism*
  • Colitis / pathology
  • Colon / metabolism*
  • Colon / pathology
  • Enteritis / metabolism
  • Enteritis / pathology
  • Female
  • Fluorescein-5-isothiocyanate
  • Fluorescent Dyes
  • Interleukin-2 / deficiency
  • Interleukin-2 / genetics
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Intestine, Small / metabolism
  • Intestine, Small / pathology
  • Mice
  • Mice, Inbred C57BL / genetics
  • Ovalbumin / metabolism
  • Reference Values

Substances

  • Antigens
  • Fluorescent Dyes
  • Interleukin-2
  • Ovalbumin
  • Fluorescein-5-isothiocyanate