August 18, 2003 | Alfonso Martín-Fontecha, Silvia Sebastiani, Uta E. Hüpken, Mariagrazia Uggucioni, Martin Lipp, Antonio Lanzavecchia, and Federica Sallusto
This study investigates the factors influencing the migration of dendritic cells (DCs) to draining lymph nodes and their impact on T cell priming. The research shows that the efficiency of DC migration varies with the number of injected DCs and that CCR7+/+ DCs, which can migrate to the lymph node, efficiently induce an increase in lymph node cellularity before T cell proliferation. Preinjection of inflammatory cytokines, such as TNF, can enhance DC migration by increasing the expression of CCL21, a chemokine that attracts CCR7+ DCs. The magnitude and quality of the CD4+ T cell response are proportional to the number of antigen-carrying DCs reaching the lymph node and can be significantly boosted by preinjection of TNF. These findings highlight the importance of DC number and tissue inflammation in DC-based vaccination. The study also reveals that DC migration can be enhanced by inflammatory stimuli through up-regulation of CCL21 on lymphatic endothelial cells, suggesting that tissue conditioning can improve T cell responses. Overall, the results emphasize the critical role of DC migration and tissue inflammation in optimizing T cell priming and vaccine efficacy.This study investigates the factors influencing the migration of dendritic cells (DCs) to draining lymph nodes and their impact on T cell priming. The research shows that the efficiency of DC migration varies with the number of injected DCs and that CCR7+/+ DCs, which can migrate to the lymph node, efficiently induce an increase in lymph node cellularity before T cell proliferation. Preinjection of inflammatory cytokines, such as TNF, can enhance DC migration by increasing the expression of CCL21, a chemokine that attracts CCR7+ DCs. The magnitude and quality of the CD4+ T cell response are proportional to the number of antigen-carrying DCs reaching the lymph node and can be significantly boosted by preinjection of TNF. These findings highlight the importance of DC number and tissue inflammation in DC-based vaccination. The study also reveals that DC migration can be enhanced by inflammatory stimuli through up-regulation of CCL21 on lymphatic endothelial cells, suggesting that tissue conditioning can improve T cell responses. Overall, the results emphasize the critical role of DC migration and tissue inflammation in optimizing T cell priming and vaccine efficacy.