Normal regulatory alpha/beta T cells effectively eliminate abnormally activated T cells lacking the interleukin 2 receptor beta in vivo

Although interleukin 2 (IL-2) has been thought to be the most important cyt okine for T cell growth, animals lacking IL-2 or a component of its recepto r molecules have more expanded T cells with activated memory phenotype, ind icating an indispensable role for the IL-2/IL-2 receptor system in regulati ng the size and activity of the T cell population. In this study, we invest igated the possible mechanism of abnormal expansion of activated T cells in IL-2 receptor beta chain (IL-2R beta)(-/-) mice using the systems of bone marrow transplantation and T cell transfer. Here, we show that IL-2R beta(- /-) T cells in mice reconstituted with a mixture of IL-2R beta(-/-) and IL- 2R beta(+/+) bone marrow cells did not develop into an abnormally activated stage, and that already activated IL-2R beta(-/-) T cells were effectively eliminated by IL-2R beta(+/+) T cells when both cells were cotransferred t o T cell-deficient host mice. This regulation and/or elimination was depend ent on T cells bearing alpha/beta type T cell receptor, especially on CD8() T cells and independent of the Fas-Fas ligand (FasL) system. IL-2R beta(/+) T cells that eliminated activated IL-2R beta(-/-) T cells expressed Fas t, perforin, granzyme B, and tumor necrosis factor alpha/beta. These result s indicate a novel function of IL-2R beta that is necessary for the inducti on of regulatory T cells acting to eliminate activated T cells.