Maturation Stages Of Dendritic Cells

DC are classified into so called 'immature' and 'mature' DC, that are distinguished by phenotype and function. 'Immature' DC can phagocytose particles [7, 8], although less efficiently than true macrophages. Furthermore, they can form large pinocytic vesicles in which extracellular fluid and solutes are sampled, a process called macropinocytosis. They express receptors that mediate adsorptive endocytosis, including C-type lectin receptors such as the mannose receptor [9] and DEC-205 [10], as well as Fey and Fee receptors. These receptors allow them to efficiently capture immune complexes and mannosylated antigens [11]. 'Immature' DC are thus well equipped to internalize and process foreign antigens, which subsequently are expressed as MHC-peptide complexes on the cell surface. In particular, macropinocytosis and receptor-mediated antigen uptake can explain why already pi-comolar or nanomolar concentrations of antigen are sufficient for presentation by DC. Yet, 'immature' DC display MHC class I and II molecules and accessory signals for T cell activation such as CD40, CD54, CD80 and CD86 only at low density. Therefore, their capacity to initiate primary immune responses in vitro is rather poor. Maturation of DC can be promoted by infectious agents or inflammatory mediators such as LPS or cytokines like IL-1, GM-CSF and TNF-a. 'Mature' DC are phenotypically characterized by downregulated Fc receptors and mannose receptors and by a reduced ability to take up and to process soluble antigens. However, these cells are now capable of triggering T cell activation by previously captured antigen mainly because they upregulate MHC class I and II molecules, costimulatory molecules including CD40, CD80 and CD86 and adhesion molecules like ICAM-1 and LFA-3.

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