De novo production of antigen-specific suppressor cells in vivo

Foxp3-expressing regulatory T cells (T-reg) play an essential role in maintaining tolerance to self antigens and are generated under physiological conditions when developing T cells encounter antigens expressed by thymic epithelial cells. We have addressed the possibility that T-reg can be exploited to prevent or even suppress ongoing immune responses to foreign antigens. To this end, one must develop methods that permit the de novo generation of T-reg specific for foreign antigens in peripheral lymphoid tissue. This report describes the methodology of generating T-reg by delivering minute doses of peptide contained in fusion Abs directed against the DEC-205 endocytic receptor on steady-state dendritic cells. The process, from cloning and production of fusion Abs to antigen-specific T-reg induction in vivo, takes similar to 2 months. The results show that delivery of T-cell receptor agonist ligands under subimmunogenic conditions represents a suitable approach for converting naive T cells into T-reg.