IFN-[gamma] expression in CD8[sup]+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4[sup]+ T cell death

• Published in: International immunology Vol. 21; no. 1; p. 73
• Main Authors: Atsumi, Toru, Sato, Masae, Kamimura, Daisuke, Moroi, Arisa, Iwakura, Yoichiro, Betz, Ulrich A K, Yoshimura, Akihiko, Nishihara, Mika, Hirano, Toshio, Murakami, Masaaki
• Format: Journal Article
• Language: English
• Published: Oxford Oxford Publishing Limited (England) 01.01.2009
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxn125

Infection with pathogens containing superantigens (Sags) can result in massive excessive CD4[sup]+ 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[sup]+ T cell death. Sag-induced CD4[sup]+ 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-γ was inversely correlated with the magnitude of IL-6 signaling, and IFN-γ deficiency inhibited Sag-induced activated CD4[sup]+ T cell death, suggesting that IL-6 suppresses CD4[sup]+ T cell death via IFN-γ expression. Interestingly, depletion of activated CD8[sup]+ T cells inhibited Sag-mediated increases in IFN-γ expression in IL-6 KO mice as well as the augmented CD4[sup]+ T cell death. The results demonstrate that IL-6-gp130-STAT3 signaling in activated CD8[sup]+ T cells contributes to Sag-induced CD4[sup]+ T cell death via IFN-γ expression, highlighting this signaling axis in CD8[sup]+ T cells as a potential therapeutic target for Sag-related syndromes.