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 SCID mice previously injected with CD4+CD45RBhigh 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-α4β7, CXCR3 and CD25 after than before culture, as well as secreting high concentrations of IL-2 and low concentrations of IFN-γ 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.
| Original language | English |
|---|---|
| Pages (from-to) | 82-93 |
| Number of pages | 12 |
| Journal | Immunology Letters |
| Volume | 156 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - 2013 Nov |
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Keywords
- CD4
- Cell culture
- IL-7
- Inflammatory bowel disease
- Memory T cells
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
IL-7 promotes long-term in vitro survival of unique long-lived memory subset generated from mucosal effector memory CD4+ T cells in chronic colitis mice. / Takahara, Masahiro; Nemoto, Yasuhiro; Oshima, Shigeru; Matsuzawa, Yu; Kanai, Takanori; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Yamamoto, Kazuhide; Watanabe, Mamoru.
In: Immunology Letters, Vol. 156, No. 1-2, 11.2013, p. 82-93.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - IL-7 promotes long-term in vitro survival of unique long-lived memory subset generated from mucosal effector memory CD4+ T cells in chronic colitis mice
AU - Takahara, Masahiro
AU - Nemoto, Yasuhiro
AU - Oshima, Shigeru
AU - Matsuzawa, Yu
AU - Kanai, Takanori
AU - Okamoto, Ryuichi
AU - Tsuchiya, Kiichiro
AU - Nakamura, Tetsuya
AU - Yamamoto, Kazuhide
AU - Watanabe, Mamoru
PY - 2013/11
Y1 - 2013/11
N2 - 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 SCID mice previously injected with CD4+CD45RBhigh 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-α4β7, CXCR3 and CD25 after than before culture, as well as secreting high concentrations of IL-2 and low concentrations of IFN-γ 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.
AB - 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 SCID mice previously injected with CD4+CD45RBhigh 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-α4β7, CXCR3 and CD25 after than before culture, as well as secreting high concentrations of IL-2 and low concentrations of IFN-γ 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.
KW - CD4
KW - Cell culture
KW - IL-7
KW - Inflammatory bowel disease
KW - Memory T cells
UR - http://www.scopus.com/inward/record.url?scp=84885996417&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885996417&partnerID=8YFLogxK
U2 - 10.1016/j.imlet.2013.09.001
DO - 10.1016/j.imlet.2013.09.001
M3 - Article
C2 - 24070768
AN - SCOPUS:84885996417
VL - 156
SP - 82
EP - 93
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
IS - 1-2
ER -