Peripheral nonresponsiveness to orally administered soluble protein antigens

The presentation of soluble model food antigens to the intestinal immune system typically induces antigen-specific systemic nonresponsiveness. Yet, the gut-associated lymphoid tissue (GALT) must launch an effective attack against potentially invasive pathogens even as it avoids mounting a response to 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 immunogenic forms of orally administered antigen elicit transient T-cell activation and proliferation. The unique microenvironment of the GALT plays a central role in determining whether functional T-cell anergy or adaptive immunity is the ultimate response. Administration of model food proteins with adjuvants (microbial products that activate the innate immune system) induces a productive immune response to this normally tolerogenic form of antigen. Recent 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 administered soluble protein antigen.