Study on the Specialized Function of Dendritic Cells

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Dendritic cells (DC) are distinctive leukocytes that are specialized antigen-presenting cells for T cell mediated immune responses. They acquire antigens in peripheral tissues and migrate to T area of lymphoid organs where they present processed peptides in context of MHC class II to T cells. In normal steady state, 2-3 distinguishable subpopulations of DC in respect of phenotype and function have been reported to locate in lymphoid organs, and it is suggested they may be different not only in maturational steps but also in developmental pathways from precursors. Therefore, we attempted to isolate T area DCs from lymph nodes and characterize phenotype and antigen-presenting and costimulatory functions. We also investigated the features of development and functional maturation of DCs in vivo and in vitro, and antigen-presenting activity after inoculating DNA encoding antigenic determinant recognized by CD4 T cells. The results obtained are 1) T area DCs present high levels of self peptides in addition to MHC class II and various adhesion and costimulatory molecules and induce apoptosis of specific T-T hybridomas, suggesting they regulate self reactivity in the periphery ; 2) Immature early-stage of DCs in which most class II are intracellular and localized to lysosomes, undergo maturation to become highly stimulatory through the intermediate stage, in which intracellular class II are found in peripheral non-lysosomal vesicles. The decrease in rate of class II degradation and increase in expression of surface class II is a fundamental feature of DCs maturation and is also exhibited by a very different population of DC ; 3) DCs isolated either from draining lymph nodes or skin present antigens to T cells and carry plasmid DNA,indicating that the uptake of DNA and/or the protein expressed by DCs triggers immune responses to DNA vaccines.