Regulation of Dendritic Cell Migration to the Draining Lymph Node

TLDR

Antigen‑pulsed dendritic cells are used as natural adjuvants for vaccination, yet the factors that determine their efficacy remain poorly understood. We examined how the dose of subcutaneously injected mature mouse dendritic cells and their CCR7 status influence migration to the draining lymph node. DC migration to lymph nodes is dose‑dependent and CCR7‑dependent, can be increased 10‑fold by inflammatory cytokines that upregulate CCL21 or 40‑fold by TNF pre‑injection, thereby amplifying CD4⁺ T‑cell responses; thus DC number and tissue inflammation are critical determinants of vaccine efficacy.

Abstract

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.