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

Abstract

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). 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. 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. 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.