IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4+ memory T cells in chronic colitis

Takayuki Tomita, Takanori Kanai, Teruji Totsuka, Yasuhiro Nemoto, Ryuichi Okamoto, Kiichiro Tsuchiya, Naoya Sakamoto, Toshiaki Ohteki, Toshifumi Hibi, Mamoru Watanabe

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We previously demonstrated that IL-7 is essential for the persistence of T-cell-mediated colitis, by showing that adoptive transfer of CD4 +CD45RBhigh T cells into IL-7-/- x RAG-1 +/+ mice did not induce colitis; and that intestinal IL-7 is not essential for this colitis model, by showing that IL-7-/- x RAG-1-/- mice parabiosed with colitic CD4+CD45RB high T-cell-transferred RAG-1-/- mice developed colitis. Here, we investigated the role of IL-7 in the maintenance of colitogenic CD4+ T cells by surgically separating these parabionts. Surprisingly, the separated IL-7-/- x RAG-1-/- mice were consistently diseased after separation, although no IL-7 mRNA was detected in the tissues of separated IL-7-/- x RAG-1-/- partners. CD4+ T cells isolated from the separated RAG-1-/- or IL-7-/- x RAG-1-/- mice were then transferred into new RAG-1-/- or IL-7-/- x RAG-1-/- mice. Regardless of the source of donor cells, RAG-1-/- recipients developed colitis, whereas IL-7 -/- x RAG-1-/- recipients did not. Collectively, these results demonstrate that IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4+ T cells rather than the maintenance of those cells in established colitic mice. They also provide a basis for the timing of IL-7/IL-7R blockade for the treatment of inflammatory bowel diseases.

Original languageEnglish
Pages (from-to)2737-2747
Number of pages11
JournalEuropean Journal of Immunology
Volume39
Issue number10
DOIs
Publication statusPublished - 2009 Oct
Externally publishedYes

Fingerprint

Interleukin-7
Lymphopenia
Colitis
T-Lymphocytes
Maintenance
Adoptive Transfer
Inflammatory Bowel Diseases

Keywords

  • Cytokines
  • Inflammation
  • Mucosa
  • Rodent
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4+ memory T cells in chronic colitis. / Tomita, Takayuki; Kanai, Takanori; Totsuka, Teruji; Nemoto, Yasuhiro; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Sakamoto, Naoya; Ohteki, Toshiaki; Hibi, Toshifumi; Watanabe, Mamoru.

In: European Journal of Immunology, Vol. 39, No. 10, 10.2009, p. 2737-2747.

Research output: Contribution to journalArticle

Tomita, T, Kanai, T, Totsuka, T, Nemoto, Y, Okamoto, R, Tsuchiya, K, Sakamoto, N, Ohteki, T, Hibi, T & Watanabe, M 2009, 'IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4+ memory T cells in chronic colitis', European Journal of Immunology, vol. 39, no. 10, pp. 2737-2747. https://doi.org/10.1002/eji.200838905
Tomita, Takayuki ; Kanai, Takanori ; Totsuka, Teruji ; Nemoto, Yasuhiro ; Okamoto, Ryuichi ; Tsuchiya, Kiichiro ; Sakamoto, Naoya ; Ohteki, Toshiaki ; Hibi, Toshifumi ; Watanabe, Mamoru. / IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4+ memory T cells in chronic colitis. In: European Journal of Immunology. 2009 ; Vol. 39, No. 10. pp. 2737-2747.
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AU - Okamoto, Ryuichi

AU - Tsuchiya, Kiichiro

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