Signaling lymphocytic activation molecule (SLAM) regulates T cellular cytotoxicity

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 engageme nt alone triggered cytotoxicity. Using H. saimiri-transformed T cells as a model system we found that SLAM-engagement promotes the release of lytic gr anules and a CD95-independent killing that requires extracellular Ca2+, cyt oskeletal rearrangements, and signaling mediated by mitogen-activated prote in kinase kinases MEK1/2. SLAM-enhanced cytotoxicity implies an immunoregul atory function by facilitating the elimination of APC and a role in overcom ing infections with pathogens requiring a cytotoxic immune response.