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

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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

Keywords

  • Cytokines
  • Inflammation
  • Mucosa
  • Rodent
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    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, 39(10), 2737-2747. https://doi.org/10.1002/eji.200838905