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

Masahiro Takahara, Yasuhiro Nemoto, Shigeru Oshima, Yu Matsuzawa, Takanori Kanai, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Kazuhide Yamamoto, Mamoru Watanabe

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish
Pages (from-to)82-93
Number of pages12
JournalImmunology Letters
Volume156
Issue number1-2
DOIs
Publication statusPublished - 2013 Nov

Fingerprint

Interleukin-7
Colitis
T-Lymphocytes
Survival
Mucous Membrane
Inflammatory Bowel Diseases
Bacterial Antigens
In Vitro Techniques
SCID Mice
Interleukin-17
Interleukin-8
Integrins
Interleukin-2
Stem Cells

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 journalArticle

Takahara, M, Nemoto, Y, Oshima, S, Matsuzawa, Y, Kanai, T, Okamoto, R, Tsuchiya, K, Nakamura, T, Yamamoto, K & Watanabe, M 2013, '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', Immunology Letters, vol. 156, no. 1-2, pp. 82-93. https://doi.org/10.1016/j.imlet.2013.09.001
Takahara, Masahiro ; Nemoto, Yasuhiro ; Oshima, Shigeru ; Matsuzawa, Yu ; Kanai, Takanori ; Okamoto, Ryuichi ; Tsuchiya, Kiichiro ; Nakamura, Tetsuya ; Yamamoto, Kazuhide ; Watanabe, Mamoru. / 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. In: Immunology Letters. 2013 ; Vol. 156, No. 1-2. pp. 82-93.
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