Transfer of antigen-specific T cells into antigen-expressing lymphopenic recipients leads to the sequential generation of Th1 and Th17 effector and protective CD25(+)FoxP3(+) regulatory cells in the periphery with surprisingly different kinetics. Such an experimental model is potentially valuable for defining the stimuli that regulate lineage decision and plasticity of various T cell effectors and peripheral regulatory T cells. Our studies have shown that IL-17 production occurs rapidly and declines within the first week with the appearance of IFN-gamma producing T cells. Regulatory T cells appear during the recovery phase of the disease. The factors that mediate this complex differentiation originating from a starting naïve T cell population remain to be defined.