The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/12/1561/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 11, December 6, 1999 1561-1572

Original Article

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

Haruhiko Suzukia, Yan Wen Zhoua, Masashi Katoa, Tak W. Makb, and Izumi Nakashimaa

a Department of Immunology, Nagoya University School of Medicine, Nagoya 466-8550, Japan
b Amgen Institute, Toronto, Ontario M5G 2C1, Canada
Department of Immunology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.81-52-744-297281-52-744-2135

k46200a{at}nucc.cc.nagoya-u.ac.jp

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-2Rβ2/– T cells in mice reconstituted with a mixture of IL-2Rβ2/– and IL-2Rβ1/+ bone marrow cells did not develop into an abnormally activated stage, and that already activated IL-2Rβ2/– T cells were effectively eliminated by IL-2Rβ1/+ 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}/β type T cell receptor, especially on CD8+ T cells and independent of the Fas–Fas ligand (FasL) system. IL-2Rβ1/+ T cells that eliminated activated IL-2Rβ2/– T cells expressed FasL, perforin, granzyme B, and tumor necrosis factor {alpha}/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.

Key Words: T lymphocytes • mice, knockout • CD8+ T lymphocytes • bone marrow transplantation • adoptive transfer

Abbreviations used in this paper: B6, C57BL/6; LCMV, lymphocytic choriomeningitis virus; RAG, recombination activating gene.

© 1999 The Rockefeller University Press


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