Modulation of the Immune Response by the Cholera-like Enterotoxins

Cholera toxins and heat labile enterotoxin from E. coli differ from most soluble proteins in eliciting systemic immunity both against themselves and unrelated admixed antigens, rather than tolerance following administration to a mucosal surface. Several reports have also demonstrated preferential induction of Th2-type responses when these molecules are used as adjuvants. Conversely, these proteins and their non-toxic derivatives, including the B sub-units are also able prevent and alleviate autoimmune diseases in naive and systemically immune hosts demonstrating wide-ranging effects on the immune system. The recent observation that amelioration of autoimmune disease is associated with the generation of regulatory T cells which inhibit pathogenic Th1 responses may also help to consolidate these two apparently contradictory outcomes of exposure to the cholera-like enterotoxins. Furthermore, the observation that EtxB is able to alleviate autoimmune disease in the absence of conjugation to autoantigen highlights its potential for use in the clinical setting where the target antigen is often unknown. Direct effects on T cells, B cells and APC have been demonstrated in vitro which have provided insights into how these molecules may elicit these diverse effects. Further investigation is required for elucidation of the mechanisms of action of adjuvanticity and tolerance induction by these molecules to realise their potential for use in vaccines and therapies for autoimmune disease in humans.