Tolerance and immunity in the intestinal immune system

The intestinal immune system must guard the body against invasion by pathog ens while avoiding a response to the many potential antigens present in foo d. In the absence of the inflammatory stimuli necessary to elicit an immune response, oral administration of soluble protein antigens induces antigen- specific systemic nonresponsiveness. Recent studies have shown that periphe ral nonresponsiveness to orally administered antigen is preceded by transie nt T-cell activation and is due primarily to the induction of functional T- cell anergy. The microenvironment of the gut-associated lymphoid tissue pla ys a central role in orally induced nonresponsiveness by supporting the gro wth of regulatory T cells that maintain intestinal homeostasis in the face of constant antigenic challenge. The transfer of nonresponsiveness by perip heral T cells from antigen-fed mice suggests that these gut-derived regulat ory cells also function in peripheral sites. When oral antigens are present ed with adjuvants (microbial products that activate the innate immune syste m) an adaptive immune response is induced to this normally tolerogenic form of antigen. This review examines recent work that has provided new insight into the regulation of tolerance and immunity in the intestinal immune sys tem.