Fig. 4.

Concept of oral tolerance induction using plant cells. A. Transgenic plant cells expressing the specific antigen are orally delivered. B. Upon release in the small intestine, the antigen (shown in green) is translocated to the gut-associated immune system (which is facilitated by use of transmucosal carrier polypeptides fused to the antigen). C. Antigen (here shown in red) accumulates in areas rich in to dendritic cells (DCs, blue). Also shown are M cells (green). D. Some of the antigen is taken up by tolerogenic CD103⁺ DCs (arrows point to antigen-loaded CD103⁺ DCs, which are shown in white, representing triple stain for antigen, CD11c, and CD103). E. As a result, antigen-specific regulatory T cells (CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁻FoxP3⁻LAP⁺ T cells) are induced. F. Induced Treg suppress B and T cell responses against the antigen, resulting in elimination of autoimmune or allergic responses. In the case of treatment for genetic disease, oral tolerance induction to the therapeutic protein suppresses formation of antidrug antibodies, so that administration of replacement therapy can correct the disease. (For inter-pretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)