DNA fragmentation and detachment of enterocytes induced by anti-CD3 mAb-activated intraepithelial lymphocytes

Kei Yaguchi, Shoichi Kayaba, Hiroyuki Soga, Mai Yamagishi, Akira Tamura, Shigeru Kasahara, Shuichi Ohara, Jo Satoh, Yoshitomo Oka, Takayoshi Toyota, Tsunetoshi Itoh

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

To elucidate the role of intraepithelial lymphocytes (IEL) and enterocytes in the defense mechanism of the small intestine, we designed experiments to stimulate the IEL by anti-CD3ε, anti-TCRαβ, or anti-TCRγδ monoclonal antibodies (mAbs), and to examine the subsequent changes to the enterocytes. The enterocytes of the duodenum and jejunum, but not of the ileum, showed massive DNA fragmentation 30 min after intraperitoneal injection of anti-CD3 mAb. These responses were also induced by anti-TCRγδ mAb, but not by anti-TCRαβ mAb, and were completely inhibited by cyclosporin A. Nearly half of the enterocytes of the villi in the duodenum and jejunum were exfoliated into the lumen 4 h after the injection of the mAb. Administration of anti-CD3 mAb also induced DNA fragmentation in Fasdeficient MRL/lpr mice, indicating that the Fas-Fas ligand system was not involved in these events. The anti-CD3 mAb treatment also induced massive DNA fragmentation in the intestinal epithelium of the duodenum and jejunum in TNF-receptor-1-deficient mice, whereas TNF-α induced only the detachment of intestinal epithelium of wild-type mice, implying the dissociation of two independent factors and/or mechanisms for DNA fragmentation and the subsequent epithelial cell detachment in the murine duodenum and jejunum. The mAb failed to exfoliate the epithelium in TNF-R1-deficient mice. Thus, TCRγδ+ IEL, when treated with anti-CD3 or anti-TCRγδ mAbs, induced rapid DNA fragmentation and subsequent detachment of the duodenal and jejunal epithelia, but not in the ileum ("the silent ileum"), partly because of the paucity of TCRγδ+ IELs in the ileum.

Original languageEnglish
Pages (from-to)71-84
Number of pages14
JournalCell and Tissue Research
Volume315
Issue number1
DOIs
Publication statusPublished - 2004 Jan 1

Keywords

  • DNA fragmentation
  • Intestinal epithelial cells
  • Intraepithelial lymphocytes
  • Mouse (female BALB/c)
  • Small intestine
  • TNF-α

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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    Yaguchi, K., Kayaba, S., Soga, H., Yamagishi, M., Tamura, A., Kasahara, S., Ohara, S., Satoh, J., Oka, Y., Toyota, T., & Itoh, T. (2004). DNA fragmentation and detachment of enterocytes induced by anti-CD3 mAb-activated intraepithelial lymphocytes. Cell and Tissue Research, 315(1), 71-84. https://doi.org/10.1007/s00441-003-0795-0