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

Background & Aims: The immunoregulatory properties of primary colonic epith elial cells (CECs) have not been defined. The ability of CECs from wild-typ e 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 (FIT C-OVA) by CECs and SIECs from wild-type and IL-2-/- mice was measured by fl ow cytometry. The effect of disrupting cytoskeleton organization and metabo lic 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 wa s used to evaluate the ability of CECs and SIECs as well as CECs from healt hy and colitic IL-2(-/-) mice to present antigen to T cells. Results: Uptak e of FITC-OVA by CECs is concentration dependent, is not saturated at physi ologic concentrations, and requires metabolically active cells. CECs from I L-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.