論文

国際誌
2011年5月

Blockade of IL-6-signaling inhibits the pathogenesis of CD4+ T cell-mediated lethal graft-versus-host reaction against minor histocompatibility antigen.

Immunology letters
  • Daisuke Noguchi
  • ,
  • Daiko Wakita
  • ,
  • Takayuki Ohkuri
  • ,
  • Masaki Tajima
  • ,
  • Kenji Chamoto
  • ,
  • Hidemitsu Kitamura
  • ,
  • Takashi Nishimura

136
2
開始ページ
146
終了ページ
55
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.imlet.2011.01.004

Graft-versus-host reaction (GVHR) is considered as a problem in hematopoietic cell transplantation. We found that CD45RB(high) CD62L(+) naïve CD4(+) T cells from wild-type B10D2 (H-2d MMTV6(-)) mice immediately differentiated into effector T cells producing high-levels of various cytokines after the transfer into BALB/c RAG2(-/-) (H-2d MMTV6(+)) mice. The expanded CD4(+) T cells, which have almost TCR Vβ3 chain, recognized the minor antigen of recipient mice and brought typical severe GVHR symptoms such as eyelid irritation, diarrhea, and liver failure. Eventually, all of the recipient mice transferred CD4(+) T cells was dead within 10 days. We demonstrated here that blockade of IL-6 signaling by administration of anti-IL-6 receptor (IL-6R) monoclonal antibody (mAb) remarkably inhibited the CD4(+) T cell-mediated lethal GVHR. In addition, we confirmed that the in vivo injection of anti-IL-6R mAb prevented the generation of effector CD4(+) T cells which produce the inflammatory cytokines such as IFN-γ, TNF-α, and IL-17. These findings indicated that IL-6 was a critical factor in the CD4(+) T cell-dependent acute GVHR induced by a minor-antigen, suggesting that IL-6-mediated signaling pathway would be a strong therapeutic target in T cell-mediated GVHR as well as other diseases including autoimmune and inflammation.

リンク情報
DOI
https://doi.org/10.1016/j.imlet.2011.01.004
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/21256159
ID情報
  • DOI : 10.1016/j.imlet.2011.01.004
  • PubMed ID : 21256159

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