Luminal CD4+ T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation

Yasuhiro Nemoto, Takanori Kanai, Tamako Shinohara, Takashi Ito, Tetsuya Nakamura, Ryuichi Okamoto, Kiichiro Tsuchiya, Martin Lipp, Yoshinobu Eishi, Mamoru Watanabe

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8 Citations (Scopus)

Abstract

Background & Aims: The egress of memory T cells from peripheral tissues, such as lung and skin, into the draining lymph nodes requires their expression of CC chemokine receptor 7 (CCR7). In the intestine, resident memory T cells in the intestinal lamina propria (LP) do not express CCR7, indicating that they are tissue bound and do not exit the intestine. Methods: We developed a cell transfer system, using rectal administration of lymphocytes to C57BL/6 mice. Lymphotoxin α-deficient mice were crossed with RAG-2-/- (recombination-activating gene-2) mice to generate lymphotoxin α-deficient × RAG-2-/- mice. Results: Severe combined immunodeficient (SCID) or RAG-2-/- mice given rectal administration of splenic CD4+ T cells from normal mice developed colitis; the cells proliferated not only in the LP but also in spleen. SCID or RAG-2-/- mice given rectal administrations of CD4+ T cells that expressed green fluorescent protein (GFP+CD4+ T cells) localized to the LP within 6 hours but were not found in the spleen until 24 hours after administration. Immunohistochemical and electron microscopic analyses detected CD4+ T cells in the intraepithelial space just 3 hours after intrarectal administration. However, neither CCR7 deficiency nor the sphingosine-1-phosphate receptor agonist Fingolimod impaired the egress of CD4+ T cells from LP to systemic circulation. Conclusions: CD4 + T cells not only penetrate from the luminal side of the intestine to the LP but also actively egress from the LP into the circulation. We developed a rectal administration system that might be used to further investigate cell trafficking in intestinal mucosa and to develop enema-based therapeutics for intestinal diseases.

Original languageEnglish
Pages (from-to)2130-2139.e11
JournalGastroenterology
Volume141
Issue number6
DOIs
Publication statusPublished - 2011 Dec

Keywords

  • Chemokine
  • Localization
  • Mouse Model
  • T-Cell Migration
  • Treatment

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Nemoto, Y., Kanai, T., Shinohara, T., Ito, T., Nakamura, T., Okamoto, R., Tsuchiya, K., Lipp, M., Eishi, Y., & Watanabe, M. (2011). Luminal CD4+ T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation. Gastroenterology, 141(6), 2130-2139.e11. https://doi.org/10.1053/j.gastro.2011.08.035