The Induction of Tolerance by Dendritic Cells That Have Captured Apoptotic Cells

Abstract

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 ImmunityMaturation 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 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).