Engagement of SLAMF2/CD48 prolongs the time frame of effective T cell activation by supporting mature dendritic cell...

Signaling lymphocyte activation molecule family (SLAMF)2/CD48 is a coactivator and adhesion molecule on cells with hematopoietic origin. It ligates mainly SLAMF4 on effector/memory CD8(+) T cells and NK cells, suggesting a potential role during viral infection, with SLAMF2 acting as a ligand to activate SLAMF4-bearing cells. The ability of SLAMF2 to signal on its own after it is engaged and the functional consequences are largely unknown. We found that cytosolic DNA-activated dendritic cells (DCs) upregulate the expression of SLAMF2 molecules. Using anti-SLAMF2 Ab and SLAMF4 recombinant protein, we found that SLAMF2 engagement activates immature DCs and, more interestingly, prolongs the survival of DNA-activated DCs by inhibiting IFN-β production and IFN-β-induced apoptosis and promotes the production of the granzyme B inhibitor protease inhibitor-9. Thus, SLAMF2 can serve as a survival molecule for DNA-activated DCs during their interaction with SLAMF4-expressing cytotoxic T cells. Based on our results, we propose that SLAMF2 engagement regulates adaptive immune responses by providing longer access of putative APCs to virus-specific effector T cells by prolonging the time frame of effective stimulation.