Functional Plasticity of Dendritic Cell Subsets as Mediated by CD40 Versus B7 Activation (original) (raw)
The Induction of Tolerance by Dendritic Cells That Have Captured Apoptotic Cells
Journal of Experimental Medicine, 2000
What makes a protein immunogenic, particularly for strong T cell-mediated immunity? To a first approximation, this determination seems to be made by dendritic cells (DCs). Immature DCs, as in skin (1-4), lung (5), blood (6, 7), and spleen (7, 8), take up proteins, immune complexes, microbes, and dying cells. However, in order to use these antigens to stimulate a T cell response, the DCs must undergo a characteristic process of terminal differentiation called "maturation." The known stimuli for DC maturation are numerous and include inflammatory cytokines, CD40 ligand (CD40L), viral and microbial constituents such as doublestranded RNA and LPS, and certain CpG oligonucleotides. DC Maturation as a Control Point in the Initiation of Immunity Maturation changes DCs in many ways that help explain their potent immunogenicity. Examples include de novo expression of T cell costimulatory molecules like CD86 (9, 10); the capacity to produce IL-12 (11, 12) and resist immunosuppression by IL-10 (13); the development of a new repertoire of chemokine receptors, especially CCR7 (14-17), that guide entry into lymphatics and migration to the T cell areas (18); the production of DC survival and stimulatory molecules like CD40 and TNF-related activation-induced cytokine receptor (TRANCE-R) (19, 20); and a redistribution of MHC class II molecules from lysosomes to the cell surface (21, 22). Recently, it has been found (Inaba, K.
Nature Immunology, 2005
The maturation status of dendritic cells (DCs) determines whether they prime or tolerize T cells. We targeted ovalbumin peptide exclusively to DCs in situ using an antibody to DEC-205 and studied the interaction of DCs with naive CD4 + T cells in tolerizing or priming conditions. We used two-photon microscopy to simultaneously track antigen-specific OT-II T cells, nonspecific T cells and DCs in lymph nodes of living mice. In both tolerance and immunity, OT-II cells arrested on DCs near high endothelial venules beginning shortly after extravasation and regained their baseline speed by 18 h. Thus, early antigen-dependent T cell arrest on DCs is a shared feature of tolerance and priming associated with activation and proliferation.