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Accumulation and activation-induced release of preformed Fas (CD95) ligand during the pathogenesis of experimental graft-versus-host disease

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2001

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Wasem, Christoph
Frutschi, Corina
Arnold, Diana
Vallan, Claudio
Lin, Tesu
Green, Douglas R.
Mueller, Christoph

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http://nbn-resolving.de/urn:nbn:de:bsz:352-142959
DOI (zitierfähiger Link)
https://doi.org/10.4049/​jimmunol.167.5.2936
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Journal of Immunology. 2001, 167(5), pp. 2936-2941. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/​jimmunol.167.5.2936

Zusammenfassung

Fas (CD95/APO-1) ligand (FasL)-mediated cytotoxicity has been implicated in tissue destruction in a variety of diseases, including acute graft-vs-host disease (GVHD). In this study, we have analyzed FasL expression and regulation during the course of experimental murine acute GVHD. Although activation-induced FasL-mediated cytotoxicity in control T cells was sensitive to the immunosuppressant cyclosporin A, we observed that functional FasL expression of GVHD T cells became increasingly cyclosporin A unresponsive. This was found to be the result of a massive in vivo accumulation and intracellular storage of FasL protein and its release in a transcription- and protein synthesis-independent manner. Immunohistochemistry analysis of FasL expression in situ revealed accumulation of FasL-expressing cells in the spleen, the liver, and small intestine, with a typical cytoplasmic and granular expression pattern. Thus, we conclude that the release of preformed FasL by infiltrating donor T cells may contribute to recipient tissue damage during the pathogenesis of acute GVHD.

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570 Biowissenschaften, Biologie

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ISO 690WASEM, Christoph, Corina FRUTSCHI, Diana ARNOLD, Claudio VALLAN, Tesu LIN, Douglas R. GREEN, Christoph MUELLER, Thomas BRUNNER, 2001. Accumulation and activation-induced release of preformed Fas (CD95) ligand during the pathogenesis of experimental graft-versus-host disease. In: Journal of Immunology. 2001, 167(5), pp. 2936-2941. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/​jimmunol.167.5.2936
BibTex
@article{Wasem2001Accum-14295,
  year={2001},
  doi={10.4049/​jimmunol.167.5.2936},
  title={Accumulation and activation-induced release of preformed Fas (CD95) ligand during the pathogenesis of experimental graft-versus-host disease},
  number={5},
  volume={167},
  issn={0022-1767},
  journal={Journal of Immunology},
  pages={2936--2941},
  author={Wasem, Christoph and Frutschi, Corina and Arnold, Diana and Vallan, Claudio and Lin, Tesu and Green, Douglas R. and Mueller, Christoph and Brunner, Thomas}
}
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