Signaling lymphocytic activation molecule (SLAM) regulates T cellular cytotoxicity |
| |
Authors: | Henning G Kraft M S Derfuss T Pirzer R de Saint-Basile G Aversa G Fleckenstein B Meinl E |
| |
Institution: | Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg, Erlangen, Germany. |
| |
Abstract: | Signaling lymphocytic activation molecule (SLAM) is a CD2-related surface receptor expressed by activated T cells and B cells. SLAM is a self ligand and enhances T cellular proliferation and IFN-gamma production. A defective SLAM associated protein (SAP) causes X-linked lymphoproliferative syndrome (XLP), a frequently lethal mononucleosis based on the inability to control EBV. We report that SLAM augments TCR-mediated cytotoxicity. In normal CD4(+) and CD8(+) T cells, SLAM enhanced TCR-mediated cytotoxicity. In CD4(+) and CD8(+) Herpesvirus saimiri (H.saimiri) infected T cells, SLAM engagement alone triggered cytotoxicity. Using H.saimiri-transformed T cells as a model system we found that SLAM-engagement promotes the release of lytic granules and a CD95-independent killing that requires extracellular Ca(2+), cytoskeletal rearrangements, and signaling mediated by mitogen-activated protein kinase kinases MEK1/2. SLAM-enhanced cytotoxicity implies an immunoregulatory function by facilitating the elimination of APC and a role in overcoming infections with pathogens requiring a cytotoxic immune response. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|