THE MUCOSAL ADJUVANT ACTIVITIES OF ADP-RIBOSYLATING BACTERIAL ENTEROTOXINS

The bacterial enterotoxins, cholera toxin and the heat labile toxin of E. coil, are well known adjuvants for mucosal immune response. Their common A chain mediates the toxigenic mechanism by causing ADP ribosyl ation of G proteins and subsequent elevation of cAMP in target cells. A large IgA and IgG antibody response to admired protein antigen (Ag) is the hallmark of these adjuvants and is clearly associated with the A chain activity. Expansion of Ag-specific B and T cells, alteration o f T cell cytokine production, and changes in regulatory T cells have b een reported as adjuvant mechanisms. The B chain derivatives of these toxins can also weakly enhance immune response, especially if covalent ly associated with Ag and used for nasophyrangeal immunization. Import antly, these toxins or their B chain derivatives can alter the normal immune regulation that produces oral tolerance. This indicates that th ey modulate mechanisms operative between the mucosal and systemic immu ne systems. There are some discrepancies between in vitro models of CT or LT activity and in vivo manifestations of their adjuvant activitie s. interpretation of current data regarding in vivo mechanism is hampe red by an incomplete understanding of how mucosal B and T cells can in teract with systemic lymphoid tissue and vice versa. More important, t here is no clear understanding of the early effects of the toxins on t he local (and draining) mucosal lymphoid tissues. This is especially t rue in the critical areas of antigen presentation, T and B cell activa tion, and cytokine production.