Staphylococcal enterotoxin A: a candidate for the amplification of physiological immunoregulatory responses in the gut

Staphylococcal enterotoxin A (SEA) is one of the bacterial products tested for modulation of unwanted immune responses. Of all the staphylococcal enterotoxins, SEA is the most potent stimulator of T cells. When administered orally, SEA acts as a superantigen (SA), producing unspecific stimulation of intra-epithelial lymphocytes (IELs) in the intestinal mucosa. This stimulation results in amplification of the normal local immunologic responses, which are mainly regulatory. This amplification is based on increased local production of IFN-γ by IELs, which acts on the nearby enterocytes. As a result, the enterocytes produce large amounts of tolerosomes, cellular corpuscles which detach themselves from the basal poles of the enterocytes and contain antigenic peptides that are conditioned to be interpreted as tolerogenic by the gut immune system. Tolerosomes are physiologically produced as a response to dietary peptides; it is already known that enterocytes posses the molecular mechanisms for processing peptides in a similar manner to lymphocytes. The fate of tolerosomes is not precisely known, but it seems that they merge with intestinal dendritic cells, conveying to them the information that orally administered peptides must be interpreted as tolerogens. SEA can stimulate this mechanism, thus favoring the development of tolerance to peptides/proteins administered subsequently via the oral route. This characteristic of SEA might be useful in therapy for regulating immune responses. The present paper reviews the current status of research regarding the impact of SEA on the enteric immune system and its potential use in the treatment of allergic and autoimmune diseases.