title: Products of anti-CD3/anti-CD28 activated lymphocytes induce differentiation and maturation of dendritic cells and have adjuvant-like activity in vitro and in vivo.
abstract: Dendritic cells (DC) orchestrate immune responses under direction of cytokines/chemokines in their microenvironment. To investigate the influence of that generated during T cell activation, we stimulated peripheral blood mononuclear cells (PBMC) with anti-CD3 and anti-CD28 coated beads and tested cell-free culture supernatants (lymphocyte conditioned medium, LCM) for cytokine/chemokine composition and biologic activity. LCM contained a battery of mediators important in the biology of myeloid (mDC) and plasmacytoid (pDC) DC. LCM differentiated monocytes into functional immature mDC, and induced maturation of immature mDC. LCM also augmented maturation and IFNalpha-production of CpG-treated pDC. Functional activity of LCM-derived DC was confirmed by their ability to enhance in vitro recall T cell responses and substantially augment in vivo cellular and humoral immune responses to various vaccines in non-human primates. These results demonstrate that products of anti-CD3/anti-CD28 stimulated PBMC generate biologically active DC in vitro and function as a vaccine adjuvant in vivo.
authors.affiliation: Department of Pathology, University of Maryland, Baltimore, USA.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Harris
authors.forename: Petra
authors.initials: P
authors.lastname: Lenz
authors.forename: Kim G
authors.initials: KG
authors.lastname: Hankey
authors.forename: Thomas
authors.initials: T
authors.lastname: MacVittie
authors.forename: Ann
authors.initials: A
authors.lastname: Farese
authors.forename: Kaori
authors.initials: K
authors.lastname: Nakajima
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hasumi
authors.forename: Dean L
authors.initials: DL
authors.lastname: Mann
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000906:Antibodies / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; C408982:CPG-oligonucleotide; D017077:Culture Media, Conditioned; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D014612:Vaccines