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-1 alpha 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.
Scheicher
C
C
Institute of Immunology, Johannes-Gutenberg-University, Mainz, Germany.
Mehlig
M
M
Dienes
H P
HP
Reske
K
K
D000818:Animals; D017951:Antigen Presentation; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis / Q000276:immunology*; D015854:Up-Regulation
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D018664:Interleukin-12