Skip Navigation


International Immunology Advance Access originally published online on May 4, 2004
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
16/6/811    most recent
dxh082v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Yamamoto, S.
Right arrow Articles by Nishimura, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamamoto, S.
Right arrow Articles by Nishimura, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

International Immunology, Vol. 16, No. 6, pp. 811-817, June 2004
© 2004 Japanese Society for Immunology

FEATURED ARTICLE OF THE MONTH

Unexpected role of TNF-{alpha} in graft versus host reaction (GVHR): donor-derived TNF-{alpha} suppresses GVHR via inhibition of IFN-{gamma}-dependent donor type-1 immunity

Satoshi Yamamoto1,2, Takemasa Tsuji1, Junko Matsuzaki1, Yue Zhange1, Kenji Chamoto1, Akemi Kosaka1, Yuji Togashi1, Kenji Sekikawa3, Ken-ichi Sawada2, Tsuguhide Takeshima1, Takao Koike2 and Takashi Nishimura1

1 Division of Immunoregulation, Institute for Genetic Medicine and 2 Department of Internal Medicine II, School of Medicine, Hokkaido University, Sapporo, Japan 3 National Institute of Animal Health, Tsukuba, Japan

Correspondence to: T. Nishimura; E-mail: tak24{at}igm.hokudai.ac.jp
Transmitting editor: T. Saito

Graft versus host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation, leading to significant morbidity and mortality. Host-derived TNF-{alpha} play a role in the induction of allo-reactive donor T cell activation and the pathogenesis of GVHD. On the other hand, the precise role of donor-derived TNF-{alpha} in GVHD remains unclear. To elucidate this issue, we designed an acute GVHD model using (B6xD2) F1 recipient mice transferred with spleen cells derived from either wild-type or TNF-{alpha}–/– C57BL/6 mice. Surprisingly, we found that spleen cells from TNF-{alpha}–/– mice induce more severe graft versus host reaction (GVHR) than wild-type spleen cells upon transfer into B6D2F1 mice. Transplantation of TNF-{alpha}–/– mouse spleen cells was associated with enhanced anti-host CTL generation and augmented deletion of host cells. Moreover, mice receiving TNF-{alpha}–/– cells showed significantly higher levels of serum IFN-{gamma}, which was mainly produced by donor CD8+ T cells. We also demonstrated that TNF-{alpha} deficiency in donor spleen cells caused a marked elevation of TNF-{alpha} producing capacity by LPS-stimulated host macrophages. Such enhanced GVHR was completely prevented by using TNF-{alpha}–/–IFN-{gamma}–/– splenic cells. Our findings demonstrate, for the first time, that donor-derived TNF-{alpha} suppress GVHR by inhibiting IFN-{gamma}-dependent donor type-1 immunity which is essential for host TNF-{alpha} elevation.

Keywords: CTL, cytokines, graft vs host disease, Th1/Th2 cells, transplantation


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.