International Immunology Advance Access originally published online on December 2, 2008
International Immunology 2009 21(1):73-80; doi:10.1093/intimm/dxn125
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IFN-
expression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death
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
Correspondence to: M. Murakami; E-mail: murakami{at}molonc.med.osaka-u.ac.jp
Infection with pathogens containing superantigens (Sags) can result in massive excessive CD4+ T cell activation and death in such conditions as toxic shock, food poisoning and autoimmune diseases. We here showed how enhancement of IL-6 signaling suppresses Sag-mediated activated CD4+ T cell death. Sag-induced CD4+ T cell death increased in IL-6 knockout (KO) mice, whereas it decreased in mice characterized by enhanced IL-6–gp130–STAT3 signaling. The serum concentration of IFN-
was inversely correlated with the magnitude of IL-6 signaling, and IFN- deficiency inhibited Sag-induced activated CD4+ T cell death, suggesting that IL-6 suppresses CD4+ T cell death via IFN- expression. Interestingly, depletion of activated CD8+ T cells inhibited Sag-mediated increases in IFN- expression in IL-6 KO mice as well as the augmented CD4+ T cell death. The results demonstrate that IL-6–gp130–STAT3 signaling in activated CD8+ T cells contributes to Sag-induced CD4+ T cell death via IFN- expression, highlighting this signaling axis in CD8+ T cells as a potential therapeutic target for Sag-related syndromes.
Keywords: CD4 T cells, CD8 T cells, IFN-, IL-6, STAT3, superantigen
* These authors contributed equally to this work
Transmitting editor: Takashi Saito
Received 20 August 2008, accepted 5 November 2008.