title: Normal regulatory alpha/beta T cells effectively eliminate abnormally activated T cells lacking the interleukin 2 receptor beta 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.
authors.affiliation: Department of Immunology, Nagoya University School of Medicine, Nagoya 466-8550, Japan. k46200a@nucc.cc.nagoya-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: Y W
authors.initials: YW
authors.lastname: Zhou
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
authors.forename: I
authors.initials: I
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016516:CD4-CD8 Ratio; D002678:Chimera; D003433:Crosses, Genetic; D016207:Cytokines / Q000235:genetics; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D018189:Immunomagnetic Separation; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2