In addition to natural thymus-derived regulatory T-cells (Tregs), peripherally-induced Tregs are of central importance in immune homeostasis. Homotypic interactions between activated effector T-cells and resting memory T-cells induced the generation of IL-10 and IFNgamma producing Tregs in vitro. This mechanism in Treg development allows new insights into T-cell vaccination, which has been employed in pilot trials of multiple sclerosis and rheumatoid arthritis with promising results.