Study on the Specialized Function of Dendritic Cells

树突状细胞（DC）是一种独特的白细胞，是T细胞介导的免疫应答的专门抗原呈递细胞。它们在外周组织中获得抗原并迁移到淋巴器官的T区，在那里它们将MHC II类背景下的加工肽呈递给T细胞。在正常稳态下，淋巴器官中存在2-3个表型和功能可区分的DC亚群，提示它们不仅在成熟阶段不同，而且在发育途径上也与前体细胞不同。因此，我们试图从淋巴结中分离T区DC并表征其表型、抗原呈递和共刺激功能。研究了DCs在体内、外的发育和功能成熟特点，以及CD 4 T细胞识别DCs抗原决定簇后DCs的抗原提呈活性。结果表明：（1）T区DCs除表达MHC Ⅱ类分子和多种粘附分子外，还表达高水平的自身多肽，并诱导特异性T-T杂交瘤细胞凋亡，提示其调节外周自身反应性; 2）DC的不成熟早期阶段，其中大多数II类是细胞内的并定位于溶酶体，经历成熟以通过中间阶段变得高度刺激，其中在外周非溶酶体囊泡中发现细胞内II类。II类降解速率的降低和表面II类表达的增加是DC成熟的基本特征，并且也由非常不同的DC群体表现出; 3）从引流淋巴结或皮肤分离的DC将抗原呈递给T细胞并携带质粒DNA，表明DC表达的DNA和/或蛋白质的摄取触发对DNA疫苗的免疫应答。

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.