Human dendritic cells : a study of early events during pathogen recognition and antigen endocytosis

Sammanfattning: The mononuclear phagocyte cell system includes monocytes, macrophages and dendritic cells which are important cells in order to recognize, ingest, destroy and also present part of a pathogen to T-lymphocytes in order to activate the adaptive immune system. Dendritic cells (DCs) stand out in their ability to stimulate T-lymphocytes and are also believed to be important to keep tolerance for “self-antigens”. Therefore DCs are of interest for use in immunotherapy studies. However in most such studies to date, DC-like cells have been used, so called monocyte derived dendritic cells (moDCs). The aim of this thesis was to investigate the early events following in vitro activation of highly purified human DCs. In the first study we observed that the production of IL-8 and down regulation of CD128b preceded surface expression of MHC class II and CD40, 80 and 86. We have in the following studies used and demonstrated the practical use of zeolite particles as ligand carriers with the purpose to study the uptake mechanisms deployed by phagocytes. We show the advantage of using zeolite particles, due to their ability to bind various types of ligands i.e. proteins, oligonucleotides, lipophilic, and hydrophobic molecules. In addition, we have adsorbed bio molecules in sequential steps, which demonstrates the potential of co adsorbing ligands e.g. for targeting a specific endosomal compartment together with molecules sensing the endosomal microenvironment. Coating zeolite particles with different biomolecules might provide further understanding of mechanisms involved in antigen sorting into endocytic compartments.