title: Natural Killer Cell Functional Activity After 4-1BB Costimulation.
abstract: Reports show enhancement of CD8 T cells' activity through CD137 (4-1BB) signal; however, not all data proved similar effect in natural killer (NK) cells. Here, the impact of 4-1BB signal on NK cells' function was assessed during short term cultures. To that end, cytokine-activated NK cells were cocultured with adenovirally transduced MCF-7 stimulator cells expressing 4-1BB ligand. Cellular cytotoxicity, cytokine production, and expression of cytotoxicity related genes were assessed after overnight cultures. Sharp decrease of CD56+ and CD56bright NK cells was demonstrated. 4-1BB neither enhanced cellular degranulation nor improved IFN-γ production although it promoted granzyme B, perforin, and FasL gene expression. 4-1BB signal stimulated higher proportions of CD56bright population to degranulate and express CD107a; however, it could not recover killing activity against K562 targets. Our data could not show major promotion in activity of all NK subpopulations. Due to great heterogeneity of NK cells, more investigation is needed to draw a comprehensive conclusion.
authors.affiliation: Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Shadi sadat
authors.initials: Ss
authors.lastname: Navabi
authors.forename: Mehrnoosh
authors.initials: M
authors.lastname: Doroudchi
authors.forename: Ahmad Hosseini
authors.initials: AH
authors.lastname: Tashnizi
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Habibagahi
mesh_terms: D053330:4-1BB Ligand / Q000494:pharmacology*; D000256:Adenoviridae / Q000235:genetics; D019002:CD56 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D053222:Fas Ligand Protein / Q000096:biosynthesis; D053804:Granzymes / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D061986:MCF-7 Cells; D054353:Perforin / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic
chemical_list: D053330:4-1BB Ligand; D019002:CD56 Antigen; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D052118:Lysosomal-Associated Membrane Protein 1; C522918:NCAM1 protein, human; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes