The immunologic tone of the intestinal tract is one of suppressed or highly regulated responses. While there are several components (intrinsic and extrinsic to the gut-associated lymphoid tissue) responsible for this immunologically suppressed tone, the intestinal epithelial call (IEC) has been proposed as a key player in this process. IECs can take up and process antigen but distinct surface molecules and restriction elements allow them to present these antigens to unique regulatory T cells. These include the expression of the class Ib molecule CD1d as well as a novel CD8 ligand, gp180. These molecules come together to activate a subpopulation of CD8+ regulatory cells whose function is to suppress immune responses in an antigen non-specific fashion most likely through cognate interactions. This form of regulation may be unique to the gut-associated lymphoid tissue which is consistent with the unusual demands upon this part of the immune system.