Distinction of class II MHC⁺ Langerhans cell-like interstitial dendritic antigen-presenting cells in murine dermis from dermal macrophages

Dermal cells are capable of initiating contact-hypersensitivity responses but the precise identification of the antigen-presenting cell within murine dermis is lacking. Class II major histocompatibility complex (MHC)⁺ cells with dendritic shape and lacking endothelial factor VIII but expressing the dendritic antigen-presenting cell marker NLDC-145 were observed in the perivascular and interstitial dermis of BALB/c and C3H/HeN skin. The heterogeneous class II MHC⁺ cells could be divided into two subsets: each was class II MHC⁺ CD45⁺ (bone marrow derived) GR-1^- (nonneutrophil/ macrophage) CD3^- (non T), but one subset was CD11b⁺ (β2 integrin) and the other was CD11b^-. Ultrastructural examination of class II MHC⁺ cells revealed the presence of a Langerhans cell-like/ indeterminant cell subset with indented nuclei, dendritic morphology, active cytoplasm, and dense intermediate filaments. Phagolysomes and Birbeck granules were not observed in such cells, indicating these were distinct from dermal macrophages and from classical epidermal Langerhans cells, respectively. Cells with a monocyte/macrophage ultrastructural appearance were also noted, likely representing the class II MHC subset expressing CD11b and Ly6c (monocyte/endothelial antigen). Dermal cells in suspension were capable of processing and presenting large protein antigens to antigen-specific T-cell hybridomas; dermal cells also induced the syngeneic mixed lymphocyte reaction. The dermal antigen-presentation activities were totally abrogated by removal of class II MHC⁺ cells, but not by removal of CD11b⁺ cells or Ly6c⁺ cells, indicating that potent antigen-presenting cell activity was restricted to the class II MHC⁺ CD11b^- Ly6c^- subset (Langerhans cell-like/indeterminant cells). In conclusion, within a complex array of dermal leukocytes a murine dermal class II MHC⁺ cell population expressing a Langerhans cell-like/ dendritic antigen-presenting cell phenotype and exhibiting potent antigen processing and presenting activity can be identified. The positioning of potent interstitial dendritic antigen-presenting cells at the interface of the vasculature with the dermal interstitium provides rapid access to an antigen-presenting cell as T cells first egress into the skin.