title: Engagement of SLAMF2/CD48 prolongs the time frame of effective T cell activation by supporting mature dendritic cell survival.
abstract: 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.
authors.affiliation: Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kis-Toth
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000071178:CD48 Antigen; D002470:Cell Survival; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: D015703:Antigens, CD; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D034741:RNA, Small Interfering