UPTAKE OF MICROPARTICLE-ADSORBED PROTEIN ANTIGEN BY BONE-MARROW-DERIVED DENDRITIC CELLS RESULTS IN UP-REGULATION OF INTERLEUKIN-1-ALPHA AND INTERLEUKIN-12 P40/P35 AND TRIGGERS PROLONGED, EFFICIENT ANTIGEN PRESENTATION

Dendritic cells synthesize and express major histocompatibility complex (MHC) class II peptide-binding elements constitutively and, therefore, belong to the category of professional antigen-presenting cells. Unlike other cells that show constitutive class II expression, such as B cells and certain T cell clones, dendritic cells possess the unique capacity to activate naive T cells. Using dendritic cells generated in vitro by culture of mouse bone marrow in the presence of low doses of recombinant mouse granulocyte/macrophage colony-stimulating factor, we found that discrete maturation stages of these cells can be distinguished which were correlated with defined functional capabilities. The striking observation was the presence of a progenitor dendritic cell expressing low levels of class II which, unlike its differentiated counterpart in vitro, possessed pronounced phagocytic activity. Adding protein antigen to dendritic cells in a particle-adsorbed form, as compared to a soluble form, we demonstrate that phagocytosis of the particle-adsorbed protein by progenitor dendritic cells involves an activation event. This is evidenced by the de novo synthesis of transcripts of interleukin-la and interleukin-12 p40/p35 as well. as transcripts of MHC class II. Most importantly, an augmented and prolonged antigen-presentation capacity was observed when the antigen was given in particle-adsorbed instead of soluble form. These findings indicate that progenitor dendritic cells are functionally more flexible and potent than fully differentiated dendritic cells and that they play a crucial role in antigen presentation. It is suggested that these findings will open up new possibilities to devise strategies for vaccine development.