期刊
IMMUNOLOGY LETTERS
卷 136, 期 2, 页码 146-155出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2011.01.004
关键词
Effector T cells; Inflammatory cytokine; Mls antigen; Th17; Treg
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology
- National Project Knowledge Cluster Initiative
- Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)
- JSPS
Graft-versus-host reaction (GVHR) is considered as a problem in hematopoietic cell transplantation. We found that CD45RB(high) CD62L(+) naive 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 V beta 3 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-gamma, TNF-alpha, 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. (C) 2011 Elsevier B.V. All rights reserved.
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