Exclusive increase of CX3CR1+CD28-CD4+ T cells in inflammatory bowel disease and their recruitment as intraepithelial lymphocytes

Taku Kobayashi, Susumu Okamoto, Yuko Iwakami, Atsushi Nakazawa, Tadakazu Hisamatsu, Hiroshi Chinen, Nobuhiko Kamada, Toshio Imai, Hidemi Goto, Toshifumi Hibi

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Abstract

Background: CX3CL1/Fractalkine (FKN) has been reported to play important roles in various inflammatory diseases. We examined the role of FKN and its receptor CX3CR1 in T-cell migration in the inflammatory bowel diseases (IBDs), ulcerative colitis (UC) and Crohn's disease (CD). Methods: CX3CR1 expression on peripheral CD4+ cells from normal controls (NL n = 24) and IBD patients (UC n = 28, CD n = 26) was examined using flow cytometry. CX3CR1 +CD4+ T cells were further characterized for surface antigens, cytokine production, and cytotoxic granule release by flow cytometry and ELISA. FKN expression in 53 colonic biopsy specimens (UC n = 20, CD n = 23, NL n = 10) was analyzed by quantitative PCR and immunohistochemistry. Isolated lamina propria and intraepithelial lymphocytes were also analyzed by flow cytometry (UC n = 10, CD n = 10, NL n = 6). Results: CX3CR1+CD4 + cells were increased in IBD while they were virtually absent in controls. Upregulation of CX3CR1 on CD4+ T cells was positively correlated with disease activity. These unique T cells expressed markers for both effector memory and cytotoxic cells. Interestingly, CX3CR1 was expressed on CD4+ T cells lacking CD28. CX3CR1+CD28 -CD4+ cells produced more IFN-γ and TNF-α than CX3CR1- counterparts and released cytotoxic granules. FKN mRNA was upregulated in inflamed colonic tissues and robust expression of FKN was immunohistochemically observed on epithelial cells. Although CX3CR1+ CD4+ cells could not be detected in the gut, CD28-CD4 + cells were found in IBD mainly as intraepithelial lymphocytes. Conclusions: FKN/CX3CR1 may contribute to the pathogenesis of IBD through the emergence of unique CX3CR1+CD28-CD4+ T cells that can act both as proinflammatory and cytotoxic cells.

Original languageEnglish
Pages (from-to)837-846
Number of pages10
JournalInflammatory bowel diseases
Volume13
Issue number7
DOIs
Publication statusPublished - 2007 Jul 1

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Keywords

  • CD28
  • CD4
  • CX3CR1
  • Fractalkine
  • Inflammatory bowel disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Kobayashi, T., Okamoto, S., Iwakami, Y., Nakazawa, A., Hisamatsu, T., Chinen, H., Kamada, N., Imai, T., Goto, H., & Hibi, T. (2007). Exclusive increase of CX3CR1+CD28-CD4+ T cells in inflammatory bowel disease and their recruitment as intraepithelial lymphocytes. Inflammatory bowel diseases, 13(7), 837-846. https://doi.org/10.1002/ibd.20113