Dendritic cells and immune responses to orally administered antigens.

The intestinal immune system discriminates between invasive pathogens and antigens that are harmless, such as food proteins and commensal bacteria. The latter groups of antigens normally induce tolerance and the nature of the intestinal immune response depends on how antigen is presented to CD4+ T cells by dendritic cells (DC). Expanding the numbers of DC in vivo using the cytokine flt3 ligand (flt3L) enhances the susceptibility of mice to the induction of oral tolerance. The relevant DC may be in Peyer's patches (PP), mesenteric lymph node (MLN) or the lamina propria (LP)of the villus mucosa. All these tissues contain a number of distinctive DC subsets, including some that can preferentially induce the differentiation of regulatory T cells. However, we find that the largest proportion of orally administered protein is taken up by DC in the lamina propria. Intestinal DC are not inherently tolerogenic. Under physiological conditions they are "quiescent", capable of presenting antigen and inducing tolerance, but being sufficiently responsive to inflammatory stimuli to allow T cell priming and protective immunity when necessary. Targeting local DC may be a useful means of inducing either tolerance or active immunity. We have achieved this using immune stimulating complexes (ISCOMS) containing Quil A, which are highly immunogenic by the oral route and appear to act by targeting DC preferentially. ISCOMS or saponins such as Quil A may prove useful adjuvants to incorporate in plant derived, mucosally active vaccines.