Antigen-bearing Langerhans cells in skin draining lymph nodes: phenotype and kinetics of migration.

Application of the fluorescent contact sensitizer Rhodamin B on mouse epidermis was used to study the migration kinetics of Langerhans cells into the draining lymph nodes. The expression of the dendritic cell markers NLDC-145 and MIDC-8 was followed over time to determine the correlation between these markers and Langerhans cell migration. In contrast with its high expression on intraepidermal Langerhans cells, the expression of NLDC-145 on dendritic cells in the draining lymph node was low at 24 h but increased at later times; in contrast, MIDC-8 expression on dendritic cells decreased. Ten days after Rhodamin B application, antigen-bearing Langerhans cells were still present in the epidermis; application of another unrelated contact sensitizer to the epidermis at this time did not lead to migration of these residual Langerhans cells. These results indicate that not all antigen-bearing Langerhans cells migrate from the skin after application of a contact sensitizer, indicating that signals in addition to simple antigen binding are necessary for migration. During this migration from epidermis to lymph nodes Langerhans cells undergo phenotypic changes. The decreased expression of the endosomal antigens MIDC-8 and MOMA-2 correlates with differentiation from predominantly antigen-processing cells to predominantly antigen-presenting cells. The reduced expression of NLDC-145 is discussed in light of a Langerhans cell-independent pathway of antigen transportation from skin to lymph node.

Oral tolerance is determined at the level of draining lymph nodes.

In the skin and in the epithelium of the oral mucosa a comparable network of Langerhans cells can be found. Antigen application on either epithelium leads to rapid emigration of Langerhans cells to the draining lymph nodes. Application on the oral mucosa leads to tolerance induction while application on the skin results in sensitization of the animal. Here we show that there are no differences in the antigen presentation capacity of oral mucosa- and skin-derived dendritic cells. However, measurement of IFN-gamma and IL-5 production, as representatives of Th1 and Th2 cytokines respectively, in total lymph node suspensions after sensitization via the skin or oral mucosa demonstrated a skewing of the response towards Th2 after antigen application on the oral mucosa. Together with our previous studies, in which it was shown that oral tolerance induction is not inherent to oral mucosa-derived dendritic cells, we postulate that oral tolerance is determined at the level of draining lymph nodes influenced by local cytokine profiles.

Dendritic cells of the oral mucosa and the induction of oral tolerance. A local affair.

The oral mucosa is an important site to induce immunological tolerance to protein antigens. Previously we have established that oral contacts to allergen can lead to systemic tolerance in both humans and experimental animals. Because of the importance of tolerance induction as a possible way to modulate allergic reactivity, we wished to study the mechanisms involved in efficient tolerance induction via the oral mucosa. Dendritic Langerhans' cells in both skin and oral epithelium are the first cells to encounter antigen. Therefore, possible functional differences between Langerhans' cells from skin and oral mucosa were studied by migration and transfer experiments. It was found that dendritic cells derived from the oral mucosa were not able to transfer tolerance, but that they acted as antigen-presenting cells in sensu stricto irrespective of the source and route of antigen administration.