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ID 52742
FullText URL
Author
Takahara, Masahiro
Nemoto, Yasuhiro
Oshima, Shigeru
Matsuzawa, Yu
Kanai, Takanori
Okamoto, Ryuichi
Tsuchiya, Kiichiro
Nakamura, Tetsuya
Watanabe, Mamoru
Abstract
Colitogenic memory CD4(+) T cells are important in the pathogenesis of inflammatory bowel disease (IBD). Although memory stem cells with high survival and self-renewal capacity were recently identified in both mice and humans, it is unclear whether a similar subset is present in chronic colitis mice. We sought to identify and purify a long-lived subset of colitogenic memory CD4(+) T cells, which may be targets for treatment of IBD. A long-lived subset of colitogenic memory CD4(+) T cells was purified using a long-term culture system. The characteristics of these cells were assessed. Interleukin (IL)-7 promoted the in vitro survival for >8 weeks of lamina propria (LP) CD4(+) T cells from colitic SOD mice previously injected with CD4(+)CD45RB(high) T cells. These cells were in a quiescent state and divided a maximum of 5 times in 4 weeks. LP CD4(+) T cells expressed higher levels of Bcl-2, integrin-alpha 4 beta 7, CXCR3 and CD25 after than before culture, as well as secreting high concentrations of IL-2 and low concentrations of IFN-gamma and IL-17 in response to intestinal bacterial antigens. LP CD4(+) T cells from colitic mice cultured with IL-7 for 8 weeks induced more severe colitis than LP CD4(+) T cells cultured for 4 weeks. We developed a novel culture system to purify a long-lived, highly pathogenic memory subset from activated LP CD4(+) T cells. IL-7 promoted long-term in vitro survival of this subset in a quiescent state. This subset will be a novel, effective target for the treatment of IBD.
Keywords
Inflammatory bowel disease
Memory T cells
CD4
IL-7
Cell culture
Published Date
2013-12
Publication Title
Immunology Letters
Volume
volume156
Issue
issue1-2
Publisher
Elsevier Science BV.
Start Page
82
End Page
93
ISSN
0165-2478
NCID
AA00231960
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52510
language
英語
Copyright Holders
© 2013 Elsevier B.V. All rights reserved.
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author
Refereed
True
DOI
Web of Sience KeyUT