Principles underlying the induction of antigen-specific regulation. (a) Mucosal tolerance. Rheumatoid arthritis (RA) self-antigen is delivered to the mucosal immune system by the oral or nasal route. If taken up and presented by the appropriate CD103+ dendritic cells (DCs), which reside in the transforming growth factor-beta (TGFβ)-rich gut lamina propria and draining lymph nodes, antigen-specific regulatory T cells (Tregs) can be induced in the presence of all-trans retinoic acid (ATRA). These Tregs should suppress RA self-antigen-specific immune responses in the joint. (b) Tolerising DC immunotherapy. DCs with tolerising capacity are generated from peripheral blood monocytes in vitro in the presence of inhibitory drugs to prevent DC activation after contact with Toll-like receptor ligands or cytokines. The DCs are then exposed to RA self-antigen and washed. The antigen-presenting DCs are injected and should induce antigen-specific Tregs in draining lymph nodes. These Tregs should suppress RA self-antigen-specific immune responses in the joint. Tolerizing DC + antigen may also be injected into joints, venous blood or lymphatics. Ag, antigen.
Thomas Arthritis Research & Therapy 2013 15:204 doi:10.1186/ar4130