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International Immunology Advance Access originally published online on March 18, 2005
International Immunology 2005 17(5):513-522; doi:10.1093/intimm/dxh231
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

Anti-CD3 induces bi-phasic apoptosis in murine intestinal epithelial cells: possible involvement of the Fas/Fas ligand system in different T cell compartments

Naoko Miura1, Masahiro Yamamoto1, Masato Fukutake1, Nobuhiro Ohtake1, Seiichi Iizuka1, Atsushi Ishige1, Hiroshi Sasaki1, Kazunori Fukuda2, Tatsuo Yamamoto3 and Satoshi Hayakawa3

1 Tsumura Research Institute, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan
2 Department of Oriental Medicine, Gifu University School of Medicine, Gifu, Japan
3 Department of Obstetrics and Gynaecology, Nihon University School of Medicine, Tokyo, Japan

Correspondence to: N. Miura; E-mail: miura_naoko{at}mail.tsumura.co.jp

Recent studies have suggested that Fas-mediated apoptosis is involved in the pathogenesis of intestinal injury. In this study, we determined the role of Fas/Fas ligand (FasL) interactions in different T cell compartments using a murine model of small intestinal injury. An intraperitoneal injection of 145-2C11 (anti-CD3) antibody into C3H/HeN, BALB/c and MRL mice induced mucosal flattening and rapid, bi-phasic intestinal epithelial cell (IEC) apoptosis, which was detected by conventional light and electron microscopy and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. In the first, early phase, villous apoptosis was observed up to 4 h after injection, and in the second, later phase, apoptotic crypt cells gradually accumulated for up to 24 h. The early and later phases of apoptosis were reduced in lpr/lpr and nude mice compared with those in control strains. In addition, the kinetics of Fas-mediated killer activity induced by the antibody injection were different between intestinal intraepithelial lymphocytes (IEL) and splenocytes (SPL) and seemed to correlate with the bi-phasic occurrence of the apoptosis. Finally, the transfer of intestinal IEL from euthymic to nude mice induced both phases of apoptosis, whereas SPL induced the second phase's crypt apoptosis only by the antibody injection. Together, these results suggest the involvement of Fas-mediated killer activity of thymus-derived T cells in different compartments. Namely, T cell populations in different compartments are differentially involved in the induction of IEC apoptosis and contribute to the complex pathogenesis of immune-mediated intestinal injury in which Fas/FasL interactions may play a critical role.

Keywords: crypt, intestinal injury, intestinal intraepithelial lymphocytes, splenocytes, villus

Transmitting editor: H. Kikutani


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