Dendritic cells (DCs) are crucial for immune responses, and their migration to draining lymph nodes is essential for T cell priming. This study investigates how the number of injected DCs and tissue inflammation influence DC migration and subsequent T cell responses. The efficiency of DC migration to the draining lymph node was found to depend on the number of injected DCs, with higher numbers leading to more efficient migration. CCR7⁺ DCs, which can migrate to the lymph node, efficiently induce an increase in lymph node cellularity, which occurs before T cell proliferation. Preinjection of inflammatory cytokines, such as TNF, increased the expression of CCL21 in lymphatic endothelial cells, enhancing DC migration. This increased migration led to a significant boost in the magnitude of CD4⁺ T cell responses. The study also shows that tissue conditioning by DCs or TNF enhances DC migration and T cell priming. CCL21 expression in lymphatic endothelial cells was upregulated after DC or TNF injection, suggesting that this is a key mechanism for increased DC recruitment. CCR7⁻/⁻ DCs, which cannot migrate to the lymph node, do not cause lymph node congestion, indicating that mature DCs reaching the lymph node are responsible for this effect. The number of DCs injected and the degree of tissue inflammation are critical factors in DC-based vaccination. The study highlights the importance of DC number and tissue inflammation in determining the effectiveness of DC-based vaccines. The findings suggest that tissue conditioning can significantly enhance T cell responses, making it a valuable strategy for improving the efficiency of DC-based vaccines.Dendritic cells (DCs) are crucial for immune responses, and their migration to draining lymph nodes is essential for T cell priming. This study investigates how the number of injected DCs and tissue inflammation influence DC migration and subsequent T cell responses. The efficiency of DC migration to the draining lymph node was found to depend on the number of injected DCs, with higher numbers leading to more efficient migration. CCR7⁺ DCs, which can migrate to the lymph node, efficiently induce an increase in lymph node cellularity, which occurs before T cell proliferation. Preinjection of inflammatory cytokines, such as TNF, increased the expression of CCL21 in lymphatic endothelial cells, enhancing DC migration. This increased migration led to a significant boost in the magnitude of CD4⁺ T cell responses. The study also shows that tissue conditioning by DCs or TNF enhances DC migration and T cell priming. CCL21 expression in lymphatic endothelial cells was upregulated after DC or TNF injection, suggesting that this is a key mechanism for increased DC recruitment. CCR7⁻/⁻ DCs, which cannot migrate to the lymph node, do not cause lymph node congestion, indicating that mature DCs reaching the lymph node are responsible for this effect. The number of DCs injected and the degree of tissue inflammation are critical factors in DC-based vaccination. The study highlights the importance of DC number and tissue inflammation in determining the effectiveness of DC-based vaccines. The findings suggest that tissue conditioning can significantly enhance T cell responses, making it a valuable strategy for improving the efficiency of DC-based vaccines.