IFN-gamma expression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death.
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-gamma was inversely correlated with the magnitude of IL-6 signaling, and IFN-gamma deficiency inhibited Sag-induced activated CD4+ T cell death, suggesting that IL-6 suppresses CD4+ T cell death via IFN-gamma expression. Interestingly, depletion of activated CD8+ T cells inhibited Sag-mediated increases in IFN-gamma 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-gamma expression, highlighting this signaling axis in CD8+ T cells as a potential therapeutic target for Sag-related syndromes.
Atsumi
Toru
T
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, Japan.
Sato
Masae
M
Kamimura
Daisuke
D
Moroi
Arisa
A
Iwakura
Yoichiro
Y
Betz
Ulrich A K
UA
Yoshimura
Akihiko
A
Nishihara
Mika
M
Hirano
Toshio
T
Murakami
Masaaki
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D018089:Superantigens / Q000276:immunology* / Q000378:metabolism
D015850:Interleukin-6; D018089:Superantigens; D007371:Interferon-gamma