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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
Yamamoto, Kazuhide ORCID Kaken ID publons
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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Refereed
True
DOI
Web of Science KeyUT