Higher concentrations of interferon-gamma enhances uptake and transport of dietary antigens by human intestinal cells: a study using cultured Caco-2 cells.

Besides functioning as a mucosal barrier and transporting nutrients, intestinal epithelial cells (IECs) also serve as antigen-presenting cells (APCs). Modification of protein antigens by proteolysis is one of the principal steps in antigen presentation to Th cells. We used a Caco-2 intestinal epithelial cell line to investigate the transepithelial transport of the dietary antigen, ovalbumin (OVA). We also examined the effects of the proinflammatory cytokine interferon-gamma (IFN-gamma) on the antigen transport process in Caco-2 cell layers. Caco-2 cell layers transferred both intact and degraded OVA from the mucosal to the serosal side. IFN-gamma stimulated OVA transport and most of the transported OVA in such cells were degraded. We also examined OVA uptake by Caco-2 cells using immunohistochemical means. Caco-2 cells incorporated OVA in a time-dependent manner and IFN-gamma significantly enhanced antigen internalization. Flow cytometry also demonstrated that IFN-gamma elevated the internalization of FITC-OVA. We also determined the effects of low and high concentrations of IFN-gamma on mucosal permeability and internalization of FITC-OVA. Although both 10 and 50 ng/mL IFN-gamma stimulated mucosal permeability to the same extent, more FITC-OVA was internalized by Caco-2 cells incubated with 50 than with 10 ng/mL IFN-gamma. These results suggest that the effects of IFN-gamma on mucosal permeability and the internalization of antigens by intestinal epithelial cells are brought about by different mechanisms. Therefore, higher concentrations of IFN-gamma stimulate the uptake, processing, and transport of dietary antigens by IECs.