Antigen handling in the intestine mediated by normal enterocytes

Abstract

The co-existence of a myriad of foreign antigens in the intestinal lumen alongside immunocompetent cells has resulted in the evolution of a specialized mucosal immune system. A natural physical barrier to antigen has been the intestinal enterocyte joined to its neighbors by desmosomes forming tight junctions. Therefore, specialized antigen sampling cells, follicle associated epithelium or M cells, were thought to be the major sites for antigen entry into the mucosa associated lymphoid tissue (MALT). However, the majority of antigens which pass through these specialized cells are large and particulate. Recently, several groups have identified the existence of a class of immunoregulatory glycoproteins, class II antigens, on normal and inflamed epithelial cells (1–3). The presence of such glycoproteins has raised questions as to the functional nature and the role that these cells might play in normal mucosal immune responses. We and others have already documented that normal enterocytes from man (4) or rat (5–6) can function as antigen presenting cells, presenting processed antigens to immunocompetent T cells. However, unlike conventional antigen presenting cells (APCs), normal enterocytes selectively activate T suppressor cells (Ts). In this paper we will identify the various features that epithelial cells possess that permit them to function as antigen presenting cells, and, furthermore, describe the findings suggesting that the induction of Ts cells relates to the presence of a novel ligand for CD8 on normal enterocytes.