title: TRANCE, a tumor necrosis factor family member, enhances the longevity and adjuvant properties of dendritic cells in vivo.
abstract: Mature dendritic cells (DCs) are powerful antigen presenting cells that have the unique capacity to migrate to the T cell zone of draining lymph nodes after subcutaneous injection. Here we report that treatment of antigen-pulsed mature DCs with tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE), a TNF family member, before immunization enhances their adjuvant capacity and elicits improved T cell priming in vivo, such that both primary and memory T cell immune responses are enhanced. By enumerating migratory DCs in the draining lymph nodes and by studying their function in stimulating naive T cells, we show that one of the underlying mechanisms for enhanced T cell responses is an increase in the number of ex vivo antigen-pulsed DCs that are found in the T cell areas of lymph nodes. These results suggest that the longevity and abundance of mature DCs at the site of T cell priming influence the strength of the DC-initiated T cell immunity in situ. Our findings have the potential to improve DC-based immunotherapy; i.e., the active immunization of humans with autologous DCs that have been pulsed with clinically significant antigens ex vivo.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021, USA.
authors.forename: R
authors.initials: R
authors.lastname: Josien
authors.forename: H L
authors.initials: HL
authors.lastname: Li
authors.forename: E
authors.initials: E
authors.lastname: Ingulli
authors.forename: S
authors.initials: S
authors.lastname: Sarma
authors.forename: B R
authors.initials: BR
authors.lastname: Wong
authors.forename: M
authors.initials: M
authors.lastname: Vologodskaia
authors.forename: R M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Y
authors.initials: Y
authors.lastname: Choi
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D023201:CD40 Ligand; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D005452:Fluoresceins; D005456:Fluorescent Dyes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007114:Immunization; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D016207:Cytokines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; C069306:5-chloromethylfluorescein; D023201:CD40 Ligand; D016178:Granulocyte-Macrophage Colony-Stimulating Factor