gms | German Medical Science

Signalling Lymphocyte Activating Molecule (SLAM; CD150) is a costimulatory receptor involved in Lymphocyte activation. SLAM is a cell surface receptor.SLAM Associated Protein (SAP;SH2D1A) a small protein with a single SH2 binding domain, has a strong affinity to activated SLAM. The SLAM SAP complex enhances Lymphocyte activation. SLAM and SAP levels peak on day 6 of effector cell cultivation on mRNA level, surface expression and protein level. One day after the SLAM and SAP peak the effector cells show their maximum cytotoxic lysis capability. Inducing of SLAM by transfection significally increased cytotoxic activity. Experiments using SLAM-Antibody coated Microspheres showed similar results. To prove that SLAM caused the increased cytotoxicity we silenced both SLAM as well as SAP using small interfering RNAs (siRNAs). Silencing of SLAM results in a reduction of surface expression of SLAM as well as decreased SLAM mRNA level. In addition the absence of SLAM in effector cells leads to a dramatically reduced cytotoxic activity when compared to untreated effector cells. Silencing of SAP does not affect the expression of SLAM , however silencing SAP has the same negative effect on effector cell cytotoxicity as the silencing of SLAM. This supports the thesis that SAP is bound to SLAM upon activation and triggers lymphocyte activation. An animal model using immunodeficient mice and a subcutaneous tumor model using COLO205 a colo-rectal carcinoma cell line was established. Seven days after inoculation the mice received stimulated effector cells. Here, we can show that the survival of the mice is increased when treated with effector cells. In conclusion we can say that SLAM and SAP are important for effector cell cytotoxicity, effector cells lacking either SLAM or SAP showed reduced cytotoxic activity, effector cells with increased SLAM levels showed an increased in cytotoxicity.