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

First Author  Miura N Year  2005
Journal  Int Immunol Volume  17
Issue  5 Pages  513-22
PubMed ID  15778290 Mgi Jnum  J:99535
Mgi Id  MGI:3582902 Doi  10.1093/intimm/dxh231
Citation  Miura N, et al. (2005) Anti-CD3 induces bi-phasic apoptosis in murine intestinal epithelial cells: possible involvement of the Fas/Fas ligand system in different T cell compartments. Int Immunol 17(5):513-22
abstractText  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.
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