Antigen handling by the epithelium and lamina propria macrophages.

The absorptive enterocyte of the small intestine expresses MHC class II antigens both constitutively and as a result of induction by cytokines. This can function to restrict antigen presentation in vitro. However, there is no direct evidence that its function in vivo is to restrict the presentation of absorbed soluble protein antigens to the available intraepithelial lymphocyte population. Alternatively, the class II molecule may be acting as a receptor for immunologically relevant antigen and transporting this antigen in a protected route across the epithelium. A third possibility concerns a possible educational role for epithelial class II. The epithelium of the intestine is identical in embryologic origin to thymic epithelium, which is known to be involved in the positive selection of alpha/beta TCR CD4-positive and CD8-positive T cells. The early development in ontogeny of epithelial and lamina propria cells expressing class II, the association of gamma/delta TCR with IEL (at least in rodents), and the reported thymus independence of these gamma/delta IEL26 all support speculation that the Ia-positive cells of the lamina propria in the fetus and the epithelium in the adult cooperate to restrict the diversity of the response to bacterial antigens and, in the antigen-free fetal state, to self-antigens. A mechanism providing constant positive selection or tolerization of T cells responsive to bacterial or food antigens would be very beneficial. The macrophage/dendritic lineage cells of the lamina propria can present antigen and modulate the response to that antigen. Because the subpopulations of these cells in the lamina propria are distinct from the antigen-handling cells of Peyer's patches, however, it is likely that the follicular and diffuse lymphoid tissues have evolved either to respond to different types of antigen or to induce and regulate different responses to the same antigen.