Rapid Up-Regulation and Granule-Independent Transport of Perforin to the Immunological Synapse Define a Novel Mechanism of Antigen-Specific CD8+ T Cell Cytotoxic Activity
- 1 May 2009
- journal article
- Published by Oxford University Press (OUP) in The Journal of Immunology
- Vol. 182 (9) , 5560-5569
- https://doi.org/10.4049/jimmunol.0803945
Abstract
CTL are endowed with the ability to eliminate pathogens through perforin-mediated cytotoxic activity. The mechanism for perforin-mediated Ag-specific killing has been solely attributed to cytotoxic granule exocytosis from activated CD8+ T cells. In this study, we redefine this mechanism, demonstrating that virus-specific CD8+ T cells rapidly up-regulate perforin in response to stimulation temporally with IFN-γ and CD107a expression. Following Ag-specific activation, newly synthesized perforin rapidly appears at the immunological synapse, both in association with and independent of cytotoxic granules, where it functions to promote cytotoxicity. Our work suggests a novel mechanism of CTL cytotoxicity and identifies a novel correlate of CD8+ T cell-mediated immunity.Keywords
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