Regulation of Dendritic Cell Migration to the Draining Lymph Node

By A. Martín-Fontecha, S. Sebastiani, U. Höpken, M. Uguccioni, M. Lipp, A. Lanzavecchia, F. Sallusto. Journal of Experimental Medicine, 2003

963 citations recorded by the source corpus.

Antigen-pulsed dendritic cells (DCs) are used as natural adjuvants for vaccination, but the factors that influence the efficacy of this treatment are poorly understood. We investigated the parameters that affect the migration of subcutaneously injected mouse-mature DCs to the draining lymph node. We found that the efficiency of DC migration varied with the number of injected DCs and that CCR7+/+ DCs migrating to the draining lymph node, but not CCR7−/− DCs that failed to do so, efficiently induced a rapid increase in lymph node cellularity, which was observed before the onset of T cell proliferation. We also report that DC migration could be increased up to 10-fold by preinjection of inflammatory cytokines that increased the expression of the CCR7 ligand CCL21 in lymphatic endothelial cells. The magnitude and quality of CD4+ T cell response was proportional to the number of antigen-carrying DCs that reached the lymph node and could be boosted up to 40-fold by preinjection of tumor necrosis factor that conditioned the tissue for increased DC migration. These results indicate that DC number and tissue inflammation are critical parameters for DC-based vaccination.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/554674130abc049e9cf431e20ec51bd53b02b35f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

Citations in the corpus

Dendritic cells: translating innate to adaptive immunity. (2006, background): “an increased expression of CCR7 on the DCs [52] as well as the corresponding chemokines, CCL19 and 21 on lymphatics and in the lymph node [53, 54].”
Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. (2004, background): “DC responsiveness to lymphatic CCL19 is supported by a second autocrine signal in the form of cysteinylated leukotrienes (186).”
Dendritic cells as therapeutic vaccines against cancer (2005, background): “In a mouse study, conditioning the injection site with TNF markedly increased both the migration of DCs to the draining lymph nodes and the magnitude of the CD4 + T-cell respons”
Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 (2018, positive): “Interestingly, these DCs may be involved at different stages during the tumor rejection process: besides their critical role for priming T cells in lymph nodes (MartIn-Fontecha et al., 2003), recent studies demonstrated that DCs can be found in tumors, where they recruit T cells and stimulate tumor-”
Dendritic-cell trafficking to lymph nodes through lymphatic vessels (2005, background): “fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1236">CCR7 ), to migrate to lymph nodes through peripheral lymphatic vessel”
Induced recruitment of NK cells to lymph nodes provides IFN-γ for TH1 priming (2004, background): “The number of DCs and their maturation state affect the efficiency of T cell priming and the quality of the developing T cell respons”
CCR7 and its ligands: balancing immunity and tolerance (2008, background): “Furthermore, DCs differentiated from the bone marrow of CCR7-deficient mice do not migrate to the draining lymph nodes following their subcutaneous injection or intra-tracheal instillatio”