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IFN-{gamma} expression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death |
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| Authors: | Atsumi, Toru Sato, Masae Kamimura, Daisuke Moroi, Arisa Iwakura, Yoichiro Betz, Ulrich A. K. Yoshimura, Akihiko Nishihara, Mika Hirano, Toshio Murakami, Masaaki |
| Affiliation: | 1 Laboratory of Developmental Immunology and the Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan 2 Laboratory of Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan 3 Laboratory Animal Research Center and the Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency, Institute of Medical Science, University of Tokyo, 108-8639 Tokyo, Japan 4 Merck KGaA, Preclinical Research & Development, 64293, Darmstadt, Germany 5 Division of Molecular and Cellular Immunology and the Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency, Medical Institute of Bioregulation, Kyushu University, 812-8582 Fukuoka, Japan |
| Abstract: | Infection with pathogens containing superantigens (Sags) canresult in massive excessive CD4+ T cell activation and deathin such conditions as toxic shock, food poisoning and autoimmunediseases. We here showed how enhancement of IL-6 signaling suppressesSag-mediated activated CD4+ T cell death. Sag-induced CD4+ Tcell death increased in IL-6 knockout (KO) mice, whereas itdecreased in mice characterized by enhanced IL-6–gp130–STAT3signaling. The serum concentration of IFN- was inversely correlatedwith the magnitude of IL-6 signaling, and IFN- deficiency inhibitedSag-induced activated CD4+ T cell death, suggesting that IL-6suppresses CD4+ T cell death via IFN- expression. Interestingly,depletion of activated CD8+ T cells inhibited Sag-mediated increasesin IFN- expression in IL-6 KO mice as well as the augmentedCD4+ T cell death. The results demonstrate that IL-6–gp130–STAT3signaling in activated CD8+ T cells contributes to Sag-inducedCD4+ T cell death via IFN- expression, highlighting this signalingaxis in CD8+ T cells as a potential therapeutic target for Sag-relatedsyndromes. |
| Keywords: | CD4 T cells CD8 T cells IFN- |
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