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Publication : CTLs contain and use intracellular stores of FasL distinct from cytolytic granules.

First Author  He JS Year  2007
Journal  J Immunol Volume  179
Issue  4 Pages  2339-48
PubMed ID  17675495 Mgi Jnum  J:151220
Mgi Id  MGI:4353010 Doi  10.4049/jimmunol.179.4.2339
Citation  He JS, et al. (2007) CTLs contain and use intracellular stores of FasL distinct from cytolytic granules. J Immunol 179(4):2339-48
abstractText  CTL lyse target cells through the release of cytolytic granule contents and cell surface expression of Fas ligand (FasL). Current models suggest that FasL is stored in cytolytic granules and that FasL cell surface expression would be subject to the same controls as degranulation. We demonstrate that murine CTLs undergo two waves of FasL cell surface expression after stimulation. The first wave is from a pre-existing pool of FasL, and the second wave requires new protein synthesis. Signaling for FasL expression appears to be finely tuned as a weak signal preferentially induced surface translocation of the stored FasL, whereas a strong signal preferentially triggered the expression of de novo synthesized FasL. The early FasL is differentially regulated from degranulation, as there were multiple circumstances whereby rapid FasL cell surface expression and FasL-dependent killing occurred in the absence of detectable degranulation. Furthermore, we found through confocal microscopy that stored FasL resides in vesicles distinct from cytolytic granules. Our data clearly show that CTL degranulation and FasL lytic mechanisms are fully independent with respect to stored component localization and regulation.
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