The thymus-derived CD4.sup.+CD25.sup.+ T cells belong to a subset of regulatory T cells potentially capable of suppressing the proliferation of pathogenic effector T cells. Intriguingly, these suppressor cells are themselves anergic, proliferating poorly to mitogenic stimulation in culture. The inventors have found that the 4-1BB co-stimulator receptor, best known for promoting the proliferation and survival of CD8.sup.+ T cells, also induces the proliferation of the CD4.sup.+CD25.sup.+ regulatory T cells both in culture and in vivo. The proliferating CD4.sup.+CD25.sup.+ T cells produce no detectable IL-2, suggesting that 4-1BB costimulation of these cells does not involve IL-2 production. The 4-1BB-expanded CD4.sup.+CD25.sup.+ T cells are functional, as they remain suppressive to other T cells in co-culture. These results support the notion that the peripheral expansion of the CD4.sup.+CD25.sup.+ T cells is controlled in part by co-stimulation.