Normal Regulatory α/β T Cells Effectively Eliminate Abnormally Activated T Cells Lacking the Interleukin 2 Receptor β in Vivo

Abstract

Although interleukin 2 (IL-2) has been thought to be the most important cytokine for T cell growth, animals lacking IL-2 or a component of its receptor molecules have more expanded T cells with activated memory phenotype, indicating an indispensable role for the IL-2/IL-2 receptor system in regulating the size and activity of the T cell population. In this study, we investigated the possible mechanism of abnormal expansion of activated T cells in IL-2 receptor beta chain (IL-2Rbeta)(-/-) mice using the systems of bone marrow transplantation and T cell transfer. Here, we show that IL-2Rbeta(2/-) T cells in mice reconstituted with a mixture of IL-2Rbeta(2/-) and IL-2Rbeta(1/+) bone marrow cells did not develop into an abnormally activated stage, and that already activated IL-2Rbeta(2/-) T cells were effectively eliminated by IL-2Rbeta(1/+) T cells when both cells were cotransferred to T cell-deficient host mice. This regulation and/or elimination was dependent 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-2Rbeta(1/+) T cells that eliminated activated IL-2Rbeta(2/-) T cells expressed FasL, perforin, granzyme B, and tumor necrosis factor alpha/beta. These results indicate a novel function of IL-2Rbeta that is necessary for the induction of regulatory T cells acting to eliminate activated T cells.