| First Author | Medana I | Year | 2001 |
| Journal | J Immunol | Volume | 167 |
| Issue | 2 | Pages | 674-81 |
| PubMed ID | 11441070 | Mgi Jnum | J:109872 |
| Mgi Id | MGI:3630048 | Doi | 10.4049/jimmunol.167.2.674 |
| Citation | Medana I, et al. (2001) Fas ligand (CD95L) protects neurons against perforin-mediated T lymphocyte cytotoxicity. J Immunol 167(2):674-81 |
| abstractText | Previous work showed that neurons of the CNS are protected against perforin-mediated T cell cytotoxicity, but are susceptible to Fas-mediated apoptosis. 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 ([Ca(2+)](i)), an indicator of cytotoxic damage. Perforin-mediated plasma membrane lysis, characterized by rapid, massive [Ca(2+)](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 [Ca(2+)](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. |
