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

Toru Atsumi, Masae Sato, Daisuke Kamimura, Arisa Moroi, Yoichiro Iwakura, Ulrich A.K. Betz, Akihiko Yoshimura, Mika Nishihara, Toshio Hirano, Masaaki Murakami

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11 Citations (Scopus)

Abstract

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-γ was inversely correlated with the magnitude of IL-6 signaling, and IFN-γ deficiency inhibited Sag-induced activated CD4+ T cell death, suggesting that IL-6 suppresses CD4+ T cell death via IFN-γ expression. Interestingly, depletion of activated CD8+ T cells inhibited Sag-mediated increases in IFN-γ 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-γ expression, highlighting this signaling axis in CD8+ T cells as a potential therapeutic target for Sag-related syndromes.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalInternational immunology
Volume21
Issue number1
DOIs
Publication statusPublished - 2009 Jan 5

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Keywords

  • CD4 T cells
  • CD8 T cells
  • IFN-γ
  • IL-6
  • STAT3
  • Superantigen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Atsumi, T., Sato, M., Kamimura, D., Moroi, A., Iwakura, Y., Betz, U. A. K., Yoshimura, A., Nishihara, M., Hirano, T., & Murakami, M. (2009). IFN-γ expression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death. International immunology, 21(1), 73-80. https://doi.org/10.1093/intimm/dxn125