TRANCE, a tumor necrosis factor family member, enhances the longevity and adjuvant properties of dendritic cells in vivo.
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.
Josien
R
R
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021, USA.
Li
H L
HL
Ingulli
E
E
Sarma
S
S
Wong
B R
BR
Vologodskaia
M
M
Steinman
R M
RM
Choi
Y
Y
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
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