Sanchez-Ruiz, Monica, Iorgu, Ana-Maria, Kuster, Florian, Hellmich, Martin ORCID: 0000-0001-5174-928X, Brunn, Anna and Deckert, Martina (2021). CD8 T cell-Derived Perforin and TNF-alpha Are Crucial Mediators of Neuronal Destruction in Experimental Autoimmune Enteric Ganglionitis. Am. J. Pathol., 191 (6). S. 1064 - 1077. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191
Full text not available from this repository.Abstract
In neuron-specific ovalbumin-transgenic CKTAC mice, antigen-specific OT-I CD8 T cells home to the enteric nervous system, where they attack and destroy neurons of the myenteric and submucosal plexus. Clinically, experimental autoimmune enteric ganglionitis (EAEG) manifests with gastrointestinal dysmotility and rapidly progresses to lethal ileus. Although interferon-g has been identified as capable of damaging neurons in EAEG, the role of perforin, Fas/FasL, and tumor necrosis factor-alpha (TNF-alpha) in this disease is still a matter of debate. Thus, CKTAC mice were adoptively transferred with either perforin(-/-) or wild-type OT-I CD8 T cells. In addition, CKTAC mice that had received wild-type OT-I CD8 T cells were treated by either anti-TNF-alpha or anti-FasL. Furthermore, wild-type OT-I CD8 T cells were adoptively transferred into CKTAC mice with neuron-specific deletion of Fas. Although neither inactivation of enteric neuronal Fas nor anti-FasL treatment improved the disease, the absence of perforin from OT-I CD8 T cells and anti-TNF-alpha treatment significantly ameliorated EAEG and prevented lethal ileus by rescue of enteric neurons. Thus, these experiments identify perforin and TNF-alpha as important in the pathogenesis of EAEG.
Item Type: | Journal Article | ||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-565131 | ||||||||||||||||||||||||||||
DOI: | 10.1016/j.ajpath.2021.02.021 | ||||||||||||||||||||||||||||
Journal or Publication Title: | Am. J. Pathol. | ||||||||||||||||||||||||||||
Volume: | 191 | ||||||||||||||||||||||||||||
Number: | 6 | ||||||||||||||||||||||||||||
Page Range: | S. 1064 - 1077 | ||||||||||||||||||||||||||||
Date: | 2021 | ||||||||||||||||||||||||||||
Publisher: | ELSEVIER SCIENCE INC | ||||||||||||||||||||||||||||
Place of Publication: | NEW YORK | ||||||||||||||||||||||||||||
ISSN: | 1525-2191 | ||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/56513 |
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