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 β chain (IL-2Rβ) -/- mice using the systems of bone marrow transplantation and T cell transfer. Here, we show that IL-2Rβ(-/-) T cells in mice reconstituted with a mixture of IL-2Rβ(-/-) and IL-2Rβ(+/+) bone marrow cells did not develop into an abnormally activated stage, and that already activated IL-2Rβ (-/-) T cells were effectively eliminated by IL-2Rβ(+/+) T cells when both cells were cotransferred to T cell-deficient host mice. This regulation and/or elimination was dependent on T cells bearing α/β type T cell receptor, especially on CD8+ T cells and independent of the Fas-Fas ligand (FasL) system. IL-2Rβ(+/+) T cells that eliminated activated IL-2Rβ(-/-) T cells expressed FasL, perforin, granzyme B, and tumor necrosis factor α/β. These results indicate a novel function of IL-2Rβ that is necessary for the induction of regulatory T cells acting to eliminate activated T cells.