論文

国際誌
2008年5月12日

IL-6-dependent spontaneous proliferation is required for the induction of colitogenic IL-17-producing CD8+ T cells.

The Journal of experimental medicine
  • Masaki Tajima
  • ,
  • Daiko Wakita
  • ,
  • Daisuke Noguchi
  • ,
  • Kenji Chamoto
  • ,
  • Zhang Yue
  • ,
  • Kazunori Fugo
  • ,
  • Harumichi Ishigame
  • ,
  • Yoichiro Iwakura
  • ,
  • Hidemitsu Kitamura
  • ,
  • Takashi Nishimura

205
5
開始ページ
1019
終了ページ
27
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1084/jem.20071133

We propose a novel role for interleukin (IL) 6 in inducing rapid spontaneous proliferation (SP) of naive CD8(+) T cells, which is a crucial step in the differentiation of colitogenic CD8(+) T cells. Homeostasis of T cells is regulated by two distinct modes of cell proliferation: major histocompatibility complex/antigen-driven rapid SP and IL-7/IL-15-dependent slow homeostatic proliferation. Using our novel model of CD8(+) T cell-dependent colitis, we found that SP of naive CD8(+) T cells is essential for inducing pathogenic cytokine-producing effector T cells. The rapid SP was predominantly induced in mesenteric lymph nodes (LNs) but not in peripheral LNs under the influence of intestinal flora and IL-6. Indeed, this SP was markedly inhibited by treatment with anti-IL-6 receptor monoclonal antibody (IL-6R mAb) or antibiotic-induced flora depletion, but not by anti-IL-7R mAb and/or in IL-15-deficient conditions. Concomitantly with the inhibition of SP, anti-IL-6R mAb significantly inhibited the induction of CD8(+) T cell-dependent autoimmune colitis. Notably, the transfer of naive CD8(+) T cells derived from IL-17(-/-) mice did not induce autoimmune colitis. Thus, we conclude that IL-6 signaling is crucial for SP under lymphopenic conditions, which subsequently caused severe IL-17-producing CD8(+) T cell-mediated autoimmune colitis. We suggest that anti-IL-6R mAb may become a promising strategy for the therapy of colitis.

リンク情報
DOI
https://doi.org/10.1084/jem.20071133
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/18426983
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373835
ID情報
  • DOI : 10.1084/jem.20071133
  • PubMed ID : 18426983
  • PubMed Central 記事ID : PMC2373835

エクスポート
BibTeX RIS