The current paradigm for antigen processing includes initial uptake by immature dendritic cells (DCs) that mature and migrate to draining lymph nodes (LNs) where they die in the course of antigen presentation. Only a few mature DCs exist in the periphery and those reportedly induce tolerance. Because only little is known about this process in the airways, we characterized the behavior and function of mature and immature DCs in murine airways.

Lung DCs were labeled by intranasal administration of FITC-dextran, and were analyzed by flow cytometry based on forward/side scatter characteristics and expression of CD11c as well as MHC Class II, CD86 and CD11b. FITC⁺ and FITC⁻ DCs were separated by FACS and analyzed for capacity to stimulate T cell proliferation.

Few FITC⁺ lung DCs (80 ± 4% of the total DCs) expressed MHC-II, CD11b, or CD86 (22 ± 3%, 5 ± 1%, 0.5 ± 0.4% of FITC⁺, respectively) and initiated proliferation in less than 1% of T cells. By contrast, FITC⁻ lung DCs frequently expressed these same maturation markers (80 ± 14%, 46 ± 12%, and 8 ± 2% of FITC⁻ cells, respectively) and induced 7.5 ± 0.4% and 1.9 ± 0.2% net proliferation in CD8 and CD4 T cells, respectively.

Murine lung contains a resident population of mature as well as immature DCs, and unexpectedly, the mature population is more capable of causing T cell proliferation. This finding suggests that the traditional paradigm for dendritic cell behavior may be reversed in the airway and implies that mature dendritic cells may also promote T cell-dependent events during airway inflammation and immunity.