In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes: relationships to maturation and role of chemokines.

Dendritic cells (DCs) are continuously transported from the intestine to mesenteric lymph nodes (MLNs). The objective of this study was to determine the migration kinetics of DCs via intestinal lymph and to investigate regulatory factors affecting their migration in vivo. DCs were obtained from spleen or thoracic duct lymph of mesenteric lymphadenectomized rats. The DCs were fluorescently labeled and injected into the subserosa of the small intestine near the cecum, and their migration patterns into MLNs were determined. Isolated DCs from intestinal lymph express intercellular adhesion molecule-1 (ICAM-1), CD11b/c, CD80/86, and major histocompatibility complex class II but maintain their ability to phagocytize latex particles, suggesting the presence of immature DCs. The isolated DCs accumulated in MLNs in a time-dependent manner with maximal accumulation at 48 h. Cytokine-induced maturation of lymph DCs did not cause a change in cell number but accelerated their transport into MLNs with a maximum at 24 h. Splenic DCs showed an intermediate level of maturation and a migration pattern similar to mature DCs. Inhibition of ICAM-1 or CD11b/c did not affect DC migration. Migration of mature DCs to MLNs was specifically blocked by desensitization of CCR7 with CCL21. In contrast, freshly isolated lymph DCs were not chemotactic for CCL21, but their migration to MLNs was mainly inhibited by desensitization of CCR6 with CCL20. The migratory ability of DCs correlates well with their degree of maturation, and different chemokine/chemokine receptor use may be the main regulator of DC migration kinetics through intestinal lymph.