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In this study, we report that Fas ligand (FasL) expression by neurons is involved in protection against perforin-mediated T cell cytotoxicity. Gene transcripts for FasL were identified in single murine hippocampal neurons by RT-PCR combined with patch clamp electrophysiology, and constitutive expression of FasL protein was confirmed in neurons by immunohistochemistry. Neurons derived from wild-type C57BL\/6 (BL6) mice and mutant BL6.gld mice lacking functional FasL were confronted with allogeneic CTLs and continuously monitored in real time for changes in levels of intracellular calcium ([Ca2+]i), an indicator of cytotoxic damage. Perforin-mediated plasma membrane lysis, characterized by rapid, massive [Ca2+]i influx into the target cells within 0.5 h, was not detected in wild-type neurons. In striking contrast, FasL-deficient neurons showed rapid increase in [Ca2+]i within 0.5 h, reflecting perforin-dependent cell lysis. FasL seems to protect neurons by blocking degranulation of CTLs, since CD3-induced release of cytotoxic granules was reduced by coapplication of Fas-specific Abs or rFasL.<\/jats:p>","DOI":"10.4049\/jimmunol.167.2.674","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T22:17:55Z","timestamp":1398118675000},"page":"674-681","source":"Crossref","is-referenced-by-count":59,"title":["Fas Ligand (CD95L) Protects Neurons Against Perforin- Mediated T Lymphocyte Cytotoxicity"],"prefix":"10.1093","volume":"167","author":[{"given":"Isabelle","family":"Medana","sequence":"first","affiliation":[{"name":"Department of Neuroimmunology, Max-Planck Institute of Neurobiology , Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Max-Planck Institute of Neurobiology , Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Flu\u0308gel","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Max-Planck Institute of Neurobiology , Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju\u0308rg","family":"Tschopp","sequence":"additional","affiliation":[{"name":"Institut de Biochimie, University of Lausanne , Epalinges ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hartmut","family":"Wekerle","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Max-Planck Institute of Neurobiology , Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Max-Planck Institute of Neurobiology , Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,7,15]]},"reference":[{"key":"2026020209045488600_R1","first-page":"1321","volume-title":"Nat. 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