Peripheral nonresponsiveness to orally administered soluble protein antigens

The presentation of soluble model food antigens to the intestinal immune sy stem typically induces antigen-specific systemic nonresponsiveness. Yet, th e gut-associated lymphoid tissue (GALT) must launch an effective attack aga inst potentially invasive pathogens even as it avoids mounting a response t o innocuous food antigens. Although the mechanism by which the GALT is able to recognize and respond to these different forms of antigen is not clear, recent studies have shown that, initially, both tolerogenic and immunogeni c forms of orally administered antigen elicit transient T-cell activation a nd proliferation. The unique microenvironment of the GALT plays a central r ole in determining whether functional T-cell anergy or adaptive immunity is the ultimate response. Administration of model food proteins with adjuvant s (microbial products that activate the innate immune system) induces a pro ductive immune response to this normally tolerogenic form of antigen. Recen t work from our laboratory has shown that an ongoing enteric infection can itself act as an adjuvant and prime for a response to an orally administere d soluble protein antigen.