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

Research output: Contribution to journalArticle

10 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
Externally publishedYes

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Superantigens
Interleukin-6
Cell Death
T-Lymphocytes
Knockout Mice
Foodborne Diseases
Septic Shock
Autoimmune Diseases

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Atsumi, T., Sato, M., Kamimura, D., Moroi, A., Iwakura, Y., Betz, U. A. K., ... 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

IFN-γ expression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death. / Atsumi, Toru; Sato, Masae; Kamimura, Daisuke; Moroi, Arisa; Iwakura, Yoichiro; Betz, Ulrich A K; Yoshimura, Akihiko; Nishihara, Mika; Hirano, Toshio; Murakami, Masaaki.

In: International Immunology, Vol. 21, No. 1, 2009, p. 73-80.

Research output: Contribution to journalArticle

Atsumi, T, Sato, M, Kamimura, D, Moroi, A, Iwakura, Y, Betz, UAK, 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, vol. 21, no. 1, pp. 73-80. https://doi.org/10.1093/intimm/dxn125
Atsumi, Toru ; Sato, Masae ; Kamimura, Daisuke ; Moroi, Arisa ; Iwakura, Yoichiro ; Betz, Ulrich A K ; Yoshimura, Akihiko ; Nishihara, Mika ; Hirano, Toshio ; Murakami, Masaaki. / IFN-γ expression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death. In: International Immunology. 2009 ; Vol. 21, No. 1. pp. 73-80.
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